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  • 1. Acharya, P.
    et al.
    Acharya, S.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Földesi, A.
    Chattopadhyaya, J.
    Tandem Electrostatic Effect from the First to the Third Aglycon in the Trimeric RNA Owing to the Nearest-Neighbor Interaction2003In: J. Am. Chem. Soc, Vol. 125, p. 2094-2100Article in journal (Refereed)
  • 2.
    Acharya, P
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, S
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Földesi, A
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Tandem electrostatic effect from the first to the third aglycon in the trimeric RNA owing to the nearest-neighbor interaction.2003In: J Am Chem Soc, ISSN 0002-7863, Vol. 125, no 8, p. 2094-100Article in journal (Other scientific)
  • 3.
    Acharya, P
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry. Department of Cell and Molecular Biology, Bioorganic Chemistry.
    Chattopadhyaya, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry. Department of Cell and Molecular Biology, Bioorganic Chemistry.
    Electrostatic Cross-modulation of the Pseudoaromatic Character in Single Stranded RNA by Nearest-neighbor interactions2005In: Pure and Applied Chemistry, Vol. 77, no 1, p. 291-311Article in journal (Refereed)
  • 4.
    Acharya, P
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    The Hydrogen Bonding and Hydration of 2'-OH in Adenosine and Adenosine 3'-ethylphosphate.2002In: J. Org. Chem., Vol. 67, p. 1852-1865Article in journal (Refereed)
  • 5. Acharya, P.
    et al.
    Cheruku, P.
    Chatterjee, S.
    Acharya, S.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J.
    Measurement of Nucleobase pKa Values in Model Mononucleotides Shows RNA-RNA Duplexes To Be More Stable than DNA-DNA Duplexes2004In: J. Am. Chem. Soc., Vol. 126, p. 2862-2869Article in journal (Refereed)
  • 6.
    Acharya, P
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Cheruku, P
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chatterjee, S
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, S
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Measurement of nucleobase pKa values in model mononucleotides shows RNA-RNA duplexes to be more stable than DNA-DNA duplexes.2004In: J Am Chem Soc, ISSN 0002-7863, Vol. 126, no 9, p. 2862-9Article in journal (Other scientific)
  • 7.
    Acharya, P
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Cheruku, P
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chatterjee, Sunanda
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Karthick Babu, S
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, S
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Measurement of nucleobase pKa values in model mononucleotides shows RNA-RNA duplexes to be more stable than DNA-DNA duplexes2004In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 126, no 9, p. 2862-2869Article in journal (Refereed)
    Abstract [en]

    To understand why the RNA-RNA duplexes in general has a higher thermodynamic stability over the corresponding DNA-DNA duplexes, we have measured the pK(a) values of both nucleoside 3',5'-bis-ethyl phosphates [Etp(d/rN)pEt] and nucleoside 3'-ethyl phosphates [(d/rN)pEt] (N = A, G, C, or T/U), modeling as donors and acceptors of base pairs in duplexes. While the 3',5'-bis-phosphates, Etp(d/rN)pEt, mimic the internucleotidic monomeric units of DNA and RNA, in which the stacking contribution is completely absent, the 3'-ethyl phosphates, (d/rN)pEt, mimic the nucleotide at the 5'-end. The pK(a) values of the nucleobase in each of these model nucleoside phosphates have been determined with low pK(a) error (sigma = +/-0.01 to 0.02) by (1)H NMR (at 500 MHz) with 20-33 different pH measurements for each compound. This study has led us to show the following: (1) All monomeric DNA nucleobases are more basic than the corresponding RNA nucleobases in their respective Etp(d/rN)pEt and (d/rN)pEt. (2) The pK(a) values of the monomeric nucleotide blocks as well as Delta pK(a) values between the donor and acceptor can be used to understand the relative base-pairing strength in the oligomeric duplexes in the RNA and DNA series. (3) The Delta G*(pKa) of the donor and acceptor of the base pair in duplexes enables a qualitative dissection of the relative strength of the base-pairing and stacking in the RNA-RNA over the DNA-DNA duplexes. (4) It is also found that the relative contribution of base-pairing strength and nucleobase stacking in RNA-RNA over DNA-DNA is mutually compensating as the % A-T/U content increases or decreases. This interdependency of stacking and hydrogen bonding can be potentially important in the molecular design of the base-pair mimics to expand the alphabet of the genetic code.

  • 8.
    Acharya, P
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Issakson, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Pradeepkumar, P.I.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Experimental Evidences Unequivocally Prove the Role of Stereoelectronics as One of the Major Forces Responsible for the Self-assembly of DNA and RNA.2002In: Collect. Czech. Chem. Commun.: Collection Symposium Series (Chemistry of Nucleic Acid Components), Vol. 5, p. 99-120Article in journal (Refereed)
  • 9.
    Acharya, P
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Nawrot, B
    Sprinzl, M
    Thibaudeau, C
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    The strength of the 3 '-gauche effect dictates the structure of 3 '-O-anthraniloyladenosine and its 5 '-phosphate, two analogues of the 3 '-end of aminoacyl-tRNA1999In: JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, ISSN 0300-9580, no 7, p. 1531-1536Article in journal (Other scientific)
    Abstract [en]

    Anthranilic acid charged yeast tRNA(Phe) or E. Coli tRNA(Val) are able to form a stable complex with EF-Tu*GTP, hence the 2'- and 3'-O-anthraniloyladenosines and their 5'-phosphate counterparts have been conceived to be the smallest units that are capable

  • 10.
    Acharya, P
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Plashkevych, O
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Morita, C
    Yamada, S
    Chattopadhyaya, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    A repertoire of pyridinium-phenyl-methyl cross-talk through a cascade of intramolecular electrostatic interactions.2003In: J Org Chem, ISSN 0022-3263, Vol. 68, no 4, p. 1529-38Article in journal (Other scientific)
  • 11.
    Acharya, P
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Thibaudeau, C
    Chattopadhyaya, J
    An energetic correlation of ab initio and NMR studies of the 3 '-gauche effect in 3 '-substituted thymidines2001In: NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, ISSN 1525-7770, Vol. 20, no 4-7, p. 1229-1233Article in journal (Refereed)
    Abstract [en]

    A straightforward correlation of our experimental NMR findings on 3'-substituted thymidine derivatives with that of the ab initio calculations shows that (i) the DeltaG(NRM)degrees (298k) of N reversible arrow S equilibrium in nucleoside can be predicted

  • 12.
    Acharya, P
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Trifonova, A
    Thibaudeau, C
    Foldesi, A
    Chattopadhyaya, J
    The transmission of the electronic character of guanin-9-yl drives the sugar-phosphate backbone torsions in guanosine 3 ',5 '-bisphosphate1999In: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, ISSN 1433-7851, Vol. 38, no 24, p. 3645-3650Article in journal (Refereed)
  • 13.
    Acharya, P
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Velikian, I
    Acharya, S
    Chattopadhyaya, J
    Molecular modelling of 2 '-OH mediated hydrogen bonding in ribonucleos(t)ides by NMR constrained AM1 and MMX calculations2001In: NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, ISSN 1525-7770, Vol. 20, no 4-7, p. 1211-1217Article in journal (Refereed)
    Abstract [en]

    The intra- and intermolecular hydrogen bonding (DeltaG(298K)degrees approximate to 2 kcal mol(-1)) of 2'-OH in nucleos(t)ides has been reported by the temperature- and concentration-dependent NMR study in conjunction with dihedral dependence of the NMR de

  • 14.
    Acharya, Parag
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Studies on the Non-covalent Interactions (Stereoelectronics, Stacking and Hydrogen Bonding) in the Self-assembly of DNA and RNA2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is based on ten publications (Papers I-X). The phosphodiester backbone makes DNA or RNA to behave as polyelectrolyte, the pentose sugar gives the flexibility, and the aglycones promote the self-assembly or the ligand-binding process. The hydrogen bonding, stacking, stereoelectronics and hydration are few of the important non-covalent forces dictating the self-assembly of DNA/RNA. The pH-dependent thermodynamics clearly show (Papers I and II) that a change of the electronic character of aglycone modulates the conformation of the sugar moiety by the tunable interplay of stereoelectronic anomeric and gauche effects, which are further transmitted to steer the sugar-phosphate backbone conformation in a cooperative manner. 3'-anthraniloyl adenosine (a mimic of 3'-teminal CCAOH of the aminoacyl-tRNAPhe) binds to EF-Tu*GTP in preference over 2'-anthraniloyl adenosine, thereby showing (Paper III) that the 2’-endo sugar conformation is a more suitable mimic of the transition state geometry than the 3’-endo conformation in discriminating between correctly and incorrectly charged aminoacyl-tRNAPhe by EF-Tu during protein synthesis. The presence of 2'-OH in RNA distinguishes it from DNA both functionally as well as structurally. This work (Paper IV) provides straightforward NMR evidence to show that the 2'-OH is intramolecularly hydrogen bonded with the vicinal 3'-oxygen, and the exposure of the 3'-phosphate of the ribonucleotides to the bulk water determines the availability of the bound water around the vicinal 2'-OH, which then can play various functional role through inter- or intramolecular interactions. The pH-dependent 1H NMR study with nicotinamide derivatives demonstrates (Paper V) that the cascade of intramolecular cation (pyridinium)-π(phenyl)-CH(methyl) interaction in edge-to-face geometry is responsible for perturbing the pKa of the pyridine-nitrogen as well as for the modulation of the aromatic character of the neighboring phenyl moiety, which is also supported by the T1 relaxation studies and ab initio calculations. It has been found (Papers VI-IX) that the variable intramolecular electrostatic interaction between electronically coupled nearest neighbor nucleobases (steered by their respective microenvironments) can modulate their respective pseudoaromatic characters. The net result of this pseudoaromatic cross-modulation is the creation of a unique set of aglycones in an oligo or polynucleotide, whose physico-chemical properties are completely dependent upon the propensity and geometry of the nearest neighbor interactions (extended genetic code). The propagation of the interplay of these electrostatic interactions across the hexameric ssDNA chain is considerably less favoured (effectively up to the fourth nucleobase) compared to that of the isosequential ssRNA (up to the sixth nucleobase). The dissection of the relative strength of basepairing and stacking in a duplex shows that stability of DNA-DNA duplex weakens over the corresponding RNA-RNA duplexes with the increasing content of A-T/U base pairs, while the strength of stacking of A-T rich DNA-DNA duplex increases in comparison with A-U rich sequence in RNA-RNA duplexes (Paper X).

    List of papers
    1. The Transmission of the Electronic Character of Guanin-9-yl Drives the Sugar-phosphate Backbone Torsions in Guanosine 3',5'-bisphosphate.
    Open this publication in new window or tab >>The Transmission of the Electronic Character of Guanin-9-yl Drives the Sugar-phosphate Backbone Torsions in Guanosine 3',5'-bisphosphate.
    Show others...
    1999 In: Angew. Chem. Int. Ed., Vol. 38, no 24, p. 3645-3650Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91143 (URN)
    Available from: 2003-11-26 Created: 2003-11-26Bibliographically approved
    2. The RNA Molecular Wire: The pH-Dependent Change in Electronic Character of Adenine-9-yl is Transmitted to Drive the Sugar-Phosphate Backbone Torsions in Adenosine 3', 5'-bisphosphate
    Open this publication in new window or tab >>The RNA Molecular Wire: The pH-Dependent Change in Electronic Character of Adenine-9-yl is Transmitted to Drive the Sugar-Phosphate Backbone Torsions in Adenosine 3', 5'-bisphosphate
    Show others...
    2000 In: J. Phys. Org. Chem., Vol. 13, p. 300-305Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91144 (URN)
    Available from: 2003-11-26 Created: 2003-11-26Bibliographically approved
    3. The Strength of the 3'-gauche effect Dictates the Structure of 3'-anthraniloyladenosine and its 5'-phosphate, Two Analogues of the 3'-end of Aminoacyl tRNA
    Open this publication in new window or tab >>The Strength of the 3'-gauche effect Dictates the Structure of 3'-anthraniloyladenosine and its 5'-phosphate, Two Analogues of the 3'-end of Aminoacyl tRNA
    Show others...
    1999 In: J. Chem. Soc. Perkin 2, p. 1531-1536Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91145 (URN)
    Available from: 2003-11-26 Created: 2003-11-26Bibliographically approved
    4. The Hydrogen Bonding and Hydration of 2'-OH in Adenosine and Adenosine 3'-ethylphosphate
    Open this publication in new window or tab >>The Hydrogen Bonding and Hydration of 2'-OH in Adenosine and Adenosine 3'-ethylphosphate
    2002 In: J. Org. Chem., Vol. 67, no 6, p. 1852-1865Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91146 (URN)
    Available from: 2003-11-26 Created: 2003-11-26Bibliographically approved
    5. A Repertoire of Pyridinium-Phenyl-Methyl Cross-Talk through a Cascade of Intramolecular Electrostatic Interactions
    Open this publication in new window or tab >>A Repertoire of Pyridinium-Phenyl-Methyl Cross-Talk through a Cascade of Intramolecular Electrostatic Interactions
    Show others...
    2003 In: J. Org. Chem., Vol. 68, no 4, p. 1529-1538Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91147 (URN)
    Available from: 2003-11-26 Created: 2003-11-26Bibliographically approved
    6. Cross-Modulation of Physicochemical Character of Aglycones in Dinucleoside (3'→5') monophosphates by the Nearest Neighbor Interaction in the Stacked State
    Open this publication in new window or tab >>Cross-Modulation of Physicochemical Character of Aglycones in Dinucleoside (3'→5') monophosphates by the Nearest Neighbor Interaction in the Stacked State
    2002 In: J. Am. Chem. Soc., Vol. 124, no 46, p. 13722-13730Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91148 (URN)
    Available from: 2003-11-26 Created: 2003-11-26Bibliographically approved
    7. Tandem Electrostatic Effect From the First to the Third Aglycon in the Trimeric RNA Owing to the Nearest-neighbor Stacking
    Open this publication in new window or tab >>Tandem Electrostatic Effect From the First to the Third Aglycon in the Trimeric RNA Owing to the Nearest-neighbor Stacking
    2003 In: J. Am. Chem. Soc., Vol. 125, no 8, p. 2094-2100Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91149 (URN)
    Available from: 2003-11-26 Created: 2003-11-26Bibliographically approved
    8. Cross-Modulation of the pKa of Nucleobases in a Single-Stranded Hexameric-RNA Due to Tandem Electrostatic Nearest-Neighbor Interactions
    Open this publication in new window or tab >>Cross-Modulation of the pKa of Nucleobases in a Single-Stranded Hexameric-RNA Due to Tandem Electrostatic Nearest-Neighbor Interactions
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    2003 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 125, no 33, p. 9948-9961Article in journal (Refereed) Published
    Abstract [en]

    The pH titration studies (pH 6.7-12.1) in a series of dimeric, trimeric, tetrameric, pentameric, and hexameric oligo-RNA molecules [GpA (2a), GpC (3a), GpApC (5), GpA(1)pA(2)pC (6), GpA(1)pA(2)pA(3)pC (7), GpA(1)pA(2)pA(3)pA(4)pC (8)] have shown that the pK(a) of N(1)-H of 9-guaninyl could be measured not only from its own deltaH8G, but also from the aromatic marker protons of other constituent nucleobases. The relative chemical shift differences [Deltadelta((N)(-)(D))] between the protons in various nucleotide residues in the oligo-RNAs at the neutral (N) and deprotonated (D) states of the guanine moiety show that the generation of the 5'-(9-guanylate ion) in oligo-RNAs 2-8 reduces the stability of the stacked helical RNA conformation owing to the destabilizing anion(G(-))-pi/dipole(Im(delta)(-)) interaction. This destabilizing effect in the deprotonated RNA is, however, opposed by the electrostatically attractive atom-pisigma (major) as well as the anion(G(-))-pi/dipole(Py(delta)(+)) (minor) interactions. Our studies have demonstrated that the electrostatically repulsive anion(G(-))-pi/dipole(Im(delta)(-)) interaction propagates from the first to the third nucleobase quite strongly in the oligo-RNAs 6-8, causing destacking of the helix, and then its effect is gradually reduced, although it is clearly NMR detectable along the RNA chain. Thus, such specific generation of a charge at a single nucleobase moiety allows us to explore the relative strength of stacking within a single-stranded helix. The pK(a) of 5'-Gp residue from its own deltaH8G in the hexameric RNA 8 is found to be 9.76 +/- 0.01; it, however, varies from 9.65 +/- 0.01 to 10.5 +/- 0.07 along the RNA chain as measured from the other marker protons (H2, H8, H5, and H6) of 9-adeninyl and 1-cytosinyl residues. This nucleobase-dependent modulation of pK(a)s (DeltapK(a) +/- 0.9) of 9-guaninyl obtained from other nucleobases in the hexameric RNA 8 represents a difference of ca. 5.1 kJ mol(-)(1), which has been attributed to the variable strength of electrostatic interactions between the electron densities of the involved atoms in the offset stacked nucleobases as well as with that of the phosphates. The chemical implication of this variable pK(a) for guanin-9-yl deprotonation as obtained from all other marker protons of each nucleotide residue within a ssRNA molecule is that it enables us to experimentally understand the variation of the electronic microenvironment around each constituent nucleobase along the RNA chain in a stepwise manner with very high accuracy without having to make any assumption. This means that the pseudoaromaticity of neighboring 9-adeninyl and next-neighbor nucleobases within a polyanionic sugar-phosphate backbone of a ssRNA can vary from one case to another due to cross-modulation of an electronically coupled pi system by a neighboring nucleobase. This modulation may depend on the sequence context, spatial proximity of the negatively charged phosphates, as well as whether the offset stacking is ON or OFF. The net outcome of this electrostatic interaction between the neighbors is creation of new sequence-dependent hybrid nucleobases in an oligo- or polynucleotide whose properties are unlike the monomeric counterpart, which may have considerable biological implications.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-91150 (URN)10.1021/ja034651h (DOI)12914458 (PubMedID)
    Available from: 2003-11-26 Created: 2003-11-26 Last updated: 2017-12-14Bibliographically approved
    9. The Nucleobases in Single-stranded DNA are Better Stacked and Yet Their Pseudoaromatic Characters are More Poorly Cross-modulated Than in the RNA Counterparts Due to Variable Tandem Nearest-neighbour Electrostatic Interactions
    Open this publication in new window or tab >>The Nucleobases in Single-stranded DNA are Better Stacked and Yet Their Pseudoaromatic Characters are More Poorly Cross-modulated Than in the RNA Counterparts Due to Variable Tandem Nearest-neighbour Electrostatic Interactions
    Show others...
    In: J. Am. Chem. Soc.Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-91151 (URN)
    Available from: 2003-11-26 Created: 2003-11-26Bibliographically approved
    10. Measurement of nucleobase pKa values in model mononucleotides shows RNA-RNA duplexes to be more stable than DNA-DNA duplexes
    Open this publication in new window or tab >>Measurement of nucleobase pKa values in model mononucleotides shows RNA-RNA duplexes to be more stable than DNA-DNA duplexes
    Show others...
    2004 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 126, no 9, p. 2862-2869Article in journal (Refereed) Published
    Abstract [en]

    To understand why the RNA-RNA duplexes in general has a higher thermodynamic stability over the corresponding DNA-DNA duplexes, we have measured the pK(a) values of both nucleoside 3',5'-bis-ethyl phosphates [Etp(d/rN)pEt] and nucleoside 3'-ethyl phosphates [(d/rN)pEt] (N = A, G, C, or T/U), modeling as donors and acceptors of base pairs in duplexes. While the 3',5'-bis-phosphates, Etp(d/rN)pEt, mimic the internucleotidic monomeric units of DNA and RNA, in which the stacking contribution is completely absent, the 3'-ethyl phosphates, (d/rN)pEt, mimic the nucleotide at the 5'-end. The pK(a) values of the nucleobase in each of these model nucleoside phosphates have been determined with low pK(a) error (sigma = +/-0.01 to 0.02) by (1)H NMR (at 500 MHz) with 20-33 different pH measurements for each compound. This study has led us to show the following: (1) All monomeric DNA nucleobases are more basic than the corresponding RNA nucleobases in their respective Etp(d/rN)pEt and (d/rN)pEt. (2) The pK(a) values of the monomeric nucleotide blocks as well as Delta pK(a) values between the donor and acceptor can be used to understand the relative base-pairing strength in the oligomeric duplexes in the RNA and DNA series. (3) The Delta G*(pKa) of the donor and acceptor of the base pair in duplexes enables a qualitative dissection of the relative strength of the base-pairing and stacking in the RNA-RNA over the DNA-DNA duplexes. (4) It is also found that the relative contribution of base-pairing strength and nucleobase stacking in RNA-RNA over DNA-DNA is mutually compensating as the % A-T/U content increases or decreases. This interdependency of stacking and hydrogen bonding can be potentially important in the molecular design of the base-pair mimics to expand the alphabet of the genetic code.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-91152 (URN)10.1021/ja0386546 (DOI)14995203 (PubMedID)
    Available from: 2003-11-26 Created: 2003-11-26 Last updated: 2017-12-14Bibliographically approved
  • 15.
    Acharya, Parag
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, Sandipta
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Cheruku, P
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Amirkhanov, N. V.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Földesi, A
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Cross-Modulation of the pKa of Nucleobases in a Single-Stranded Hexameric-RNA Due to Tandem Electrostatic Nearest-Neighbor Interactions2003In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 125, no 33, p. 9948-9961Article in journal (Refereed)
    Abstract [en]

    The pH titration studies (pH 6.7-12.1) in a series of dimeric, trimeric, tetrameric, pentameric, and hexameric oligo-RNA molecules [GpA (2a), GpC (3a), GpApC (5), GpA(1)pA(2)pC (6), GpA(1)pA(2)pA(3)pC (7), GpA(1)pA(2)pA(3)pA(4)pC (8)] have shown that the pK(a) of N(1)-H of 9-guaninyl could be measured not only from its own deltaH8G, but also from the aromatic marker protons of other constituent nucleobases. The relative chemical shift differences [Deltadelta((N)(-)(D))] between the protons in various nucleotide residues in the oligo-RNAs at the neutral (N) and deprotonated (D) states of the guanine moiety show that the generation of the 5'-(9-guanylate ion) in oligo-RNAs 2-8 reduces the stability of the stacked helical RNA conformation owing to the destabilizing anion(G(-))-pi/dipole(Im(delta)(-)) interaction. This destabilizing effect in the deprotonated RNA is, however, opposed by the electrostatically attractive atom-pisigma (major) as well as the anion(G(-))-pi/dipole(Py(delta)(+)) (minor) interactions. Our studies have demonstrated that the electrostatically repulsive anion(G(-))-pi/dipole(Im(delta)(-)) interaction propagates from the first to the third nucleobase quite strongly in the oligo-RNAs 6-8, causing destacking of the helix, and then its effect is gradually reduced, although it is clearly NMR detectable along the RNA chain. Thus, such specific generation of a charge at a single nucleobase moiety allows us to explore the relative strength of stacking within a single-stranded helix. The pK(a) of 5'-Gp residue from its own deltaH8G in the hexameric RNA 8 is found to be 9.76 +/- 0.01; it, however, varies from 9.65 +/- 0.01 to 10.5 +/- 0.07 along the RNA chain as measured from the other marker protons (H2, H8, H5, and H6) of 9-adeninyl and 1-cytosinyl residues. This nucleobase-dependent modulation of pK(a)s (DeltapK(a) +/- 0.9) of 9-guaninyl obtained from other nucleobases in the hexameric RNA 8 represents a difference of ca. 5.1 kJ mol(-)(1), which has been attributed to the variable strength of electrostatic interactions between the electron densities of the involved atoms in the offset stacked nucleobases as well as with that of the phosphates. The chemical implication of this variable pK(a) for guanin-9-yl deprotonation as obtained from all other marker protons of each nucleotide residue within a ssRNA molecule is that it enables us to experimentally understand the variation of the electronic microenvironment around each constituent nucleobase along the RNA chain in a stepwise manner with very high accuracy without having to make any assumption. This means that the pseudoaromaticity of neighboring 9-adeninyl and next-neighbor nucleobases within a polyanionic sugar-phosphate backbone of a ssRNA can vary from one case to another due to cross-modulation of an electronically coupled pi system by a neighboring nucleobase. This modulation may depend on the sequence context, spatial proximity of the negatively charged phosphates, as well as whether the offset stacking is ON or OFF. The net outcome of this electrostatic interaction between the neighbors is creation of new sequence-dependent hybrid nucleobases in an oligo- or polynucleotide whose properties are unlike the monomeric counterpart, which may have considerable biological implications.

  • 16.
    Acharya, S.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, P.
    Földesi, A.
    Chattopadhyaya, J.
    Cross-Modulation of Physicochemical Character of Aglycones in Dinucleoside (3'→5') Monophosphates by the Nearest Neighbor Interaction in the Stacked State2002In: J. Am. Chem. Soc., Vol. 124, p. 13722-13730Article in journal (Refereed)
  • 17.
    Acharya, S
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, P
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Földesi, A
    Chattopadhyaya, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Cross-modulation of physicochemical character of aglycones in dinucleoside (3'-->5') monophosphates by the nearest neighbor interaction in the stacked state.2002In: J Am Chem Soc, ISSN 0002-7863, Vol. 124, no 46, p. 13722-30Article in journal (Other scientific)
  • 18.
    Acharya, S.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Barman, J.
    Cheruku, P.
    Chatterjee, S.
    Acharya, P.
    Isaksson, J.
    Chattopadhyaya, J.
    Significant pKa Perturbation of Nucleobases Is an Intrinsic Property of the Sequence Context in DNA and RNA2004In: J. Am. Chem. Soc., Vol. 126, p. 8674-8681Article in journal (Refereed)
  • 19.
    Acharya, S.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Földesi, A.
    Chattopadhyaya, J.
    The pKa of the Internucleotidic 2'-Hydroxyl Group in Diribonucleoside (3'→5') Monophosphates2003In: J. Org. Chem., Vol. 68, p. 1906-1910Article in journal (Refereed)
  • 20.
    Acharya, S
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Földesi, A
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    The pK(a) of the internucleotidic 2'-hydroxyl group in diribonucleoside (3'-->5') monophosphates.2003In: J Org Chem, ISSN 0022-3263, Vol. 68, no 5, p. 1906-10Article in journal (Other scientific)
  • 21.
    Acharya, Sandipta
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Some Aspects of Physicochemical Properties of DNA and RNA2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is based on nine research publications (I – IX) on structure and reactivity of RNA vis-à-vis DNA. The DNA and RNA are made of flexible pentose sugar units, polyelectrolytic phosphodiester backbone, and heterocyclic nucleobases. DNA stores our genetic code, whereas RNA is involved both in protein biosynthesis and catalysis. Various ligand-binding and recognition properties of DNA/RNA are mediated through inter- and intra-molecular H-bonding and stacking interactions, beside hydration, van der Waal and London dispersion forces. In this work the pH dependant chemical shift, pKa values of 2'-OH group as well as those the nucleobases in different sequence context, alkaline hydrolysis of the internucleotidic phosphodiester bonds and analysis of NOESY footprints along with NMR constrained molecular dynamics simulation were used as tools to explore and understand the physico-chemical behavior of various nucleic acid sequences, and the forces involved in their self-assembly process. Papers I – II showed that the ionization of 2'-OH group is nucleobase-dependant. Paper III showed that the chemical characters of internucleotidic phosphate are non-identical in RNA compared to that of DNA. Papers IV – VI show that variable intramolecular electrostatic interactions between electronically coupled nearest neighbor nucleobases in a ssRNA can modulate their respective pseudoaromatic character, and result in creation of a unique set of aglycons with unique properties depending on propensity and geometry of nearest neighbor interaction. Paper VII showed that the cross-modulation of the pseudoaromatic character of nucleobases by the nearest neighbor is sequence-dependant in nature in oligonucleotides. Paper VIII showed that the purine-rich hexameric ssDNA and ssRNA retain the right-handed helical structure (B-type in ssDNA and A-type in ssRNA) in the single-stranded form even in absence of intermolecular hydrogen bonding. The directionality of stacking geometry however differs in ssDNA compared to ssRNA. In ssDNA the relatively electron-rich imidazole stacks above the electron-deficient pyrimidine in the 5' to 3' direction, in contradistinction, the pyrimidine stacks above the imidazole in the 5' to 3' direction in ssRNA. Paper IX showed that the pKa values of the nucleobases in monomeric nucleotides can be used to show that a RNA-RNA duplex is more stable than a DNA-DNA duplex. The dissection of the relative strength of base-pairing and stacking showed that the relative contribution of former compared to that of the latter in an RNA-RNA over the corresponding DNA-DNA duplexes decreases with the increasing content of A-T/U base pairs in a sequence.

    List of papers
    1. The pKa’s of 2'-Hydroxyl Group in Nucleosides and Nucleotides
    Open this publication in new window or tab >>The pKa’s of 2'-Hydroxyl Group in Nucleosides and Nucleotides
    Show others...
    2001 In: J. Am. Chem. Soc., Vol. 123, p. 2893-2894Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94240 (URN)
    Available from: 2006-04-07 Created: 2006-04-07 Last updated: 2014-03-03Bibliographically approved
    2. The pKa of the Internucleotidic 2'-Hydroxyl Group in Diribonucleoside (3'→5') Monophosphates
    Open this publication in new window or tab >>The pKa of the Internucleotidic 2'-Hydroxyl Group in Diribonucleoside (3'→5') Monophosphates
    2003 In: J. Org. Chem., Vol. 68, p. 1906-1910Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94241 (URN)
    Available from: 2006-04-07 Created: 2006-04-07Bibliographically approved
    3. Non-identical electronic characters of the internucleotidic pohosphates in RNA modulate the chemical reactivity of the phosphodiester bonds
    Open this publication in new window or tab >>Non-identical electronic characters of the internucleotidic pohosphates in RNA modulate the chemical reactivity of the phosphodiester bonds
    Show others...
    2006 In: Org. Biomol. Chem., Vol. 4, p. 928-941Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94242 (URN)
    Available from: 2006-04-07 Created: 2006-04-07Bibliographically approved
    4. Cross-Modulation of Physicochemical Character of Aglycones in Dinucleoside (3'→5') Monophosphates by the Nearest Neighbor Interaction in the Stacked State
    Open this publication in new window or tab >>Cross-Modulation of Physicochemical Character of Aglycones in Dinucleoside (3'→5') Monophosphates by the Nearest Neighbor Interaction in the Stacked State
    2002 In: J. Am. Chem. Soc., Vol. 124, p. 13722-13730Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94243 (URN)
    Available from: 2006-04-07 Created: 2006-04-07Bibliographically approved
    5. Tandem Electrostatic Effect from the First to the Third Aglycon in the Trimeric RNA Owing to the Nearest-Neighbor Interaction
    Open this publication in new window or tab >>Tandem Electrostatic Effect from the First to the Third Aglycon in the Trimeric RNA Owing to the Nearest-Neighbor Interaction
    2003 In: J. Am. Chem. Soc, Vol. 125, p. 2094-2100Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94244 (URN)
    Available from: 2006-04-07 Created: 2006-04-07Bibliographically approved
    6. Cross-Modulation of the pKa of Nucleobases in a Single-Stranded Hexameric-RNA Due to Tandem Electrostatic Nearest-Neighbor Interactions
    Open this publication in new window or tab >>Cross-Modulation of the pKa of Nucleobases in a Single-Stranded Hexameric-RNA Due to Tandem Electrostatic Nearest-Neighbor Interactions
    Show others...
    2003 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 125, no 33, p. 9948-9961Article in journal (Refereed) Published
    Abstract [en]

    The pH titration studies (pH 6.7-12.1) in a series of dimeric, trimeric, tetrameric, pentameric, and hexameric oligo-RNA molecules [GpA (2a), GpC (3a), GpApC (5), GpA(1)pA(2)pC (6), GpA(1)pA(2)pA(3)pC (7), GpA(1)pA(2)pA(3)pA(4)pC (8)] have shown that the pK(a) of N(1)-H of 9-guaninyl could be measured not only from its own deltaH8G, but also from the aromatic marker protons of other constituent nucleobases. The relative chemical shift differences [Deltadelta((N)(-)(D))] between the protons in various nucleotide residues in the oligo-RNAs at the neutral (N) and deprotonated (D) states of the guanine moiety show that the generation of the 5'-(9-guanylate ion) in oligo-RNAs 2-8 reduces the stability of the stacked helical RNA conformation owing to the destabilizing anion(G(-))-pi/dipole(Im(delta)(-)) interaction. This destabilizing effect in the deprotonated RNA is, however, opposed by the electrostatically attractive atom-pisigma (major) as well as the anion(G(-))-pi/dipole(Py(delta)(+)) (minor) interactions. Our studies have demonstrated that the electrostatically repulsive anion(G(-))-pi/dipole(Im(delta)(-)) interaction propagates from the first to the third nucleobase quite strongly in the oligo-RNAs 6-8, causing destacking of the helix, and then its effect is gradually reduced, although it is clearly NMR detectable along the RNA chain. Thus, such specific generation of a charge at a single nucleobase moiety allows us to explore the relative strength of stacking within a single-stranded helix. The pK(a) of 5'-Gp residue from its own deltaH8G in the hexameric RNA 8 is found to be 9.76 +/- 0.01; it, however, varies from 9.65 +/- 0.01 to 10.5 +/- 0.07 along the RNA chain as measured from the other marker protons (H2, H8, H5, and H6) of 9-adeninyl and 1-cytosinyl residues. This nucleobase-dependent modulation of pK(a)s (DeltapK(a) +/- 0.9) of 9-guaninyl obtained from other nucleobases in the hexameric RNA 8 represents a difference of ca. 5.1 kJ mol(-)(1), which has been attributed to the variable strength of electrostatic interactions between the electron densities of the involved atoms in the offset stacked nucleobases as well as with that of the phosphates. The chemical implication of this variable pK(a) for guanin-9-yl deprotonation as obtained from all other marker protons of each nucleotide residue within a ssRNA molecule is that it enables us to experimentally understand the variation of the electronic microenvironment around each constituent nucleobase along the RNA chain in a stepwise manner with very high accuracy without having to make any assumption. This means that the pseudoaromaticity of neighboring 9-adeninyl and next-neighbor nucleobases within a polyanionic sugar-phosphate backbone of a ssRNA can vary from one case to another due to cross-modulation of an electronically coupled pi system by a neighboring nucleobase. This modulation may depend on the sequence context, spatial proximity of the negatively charged phosphates, as well as whether the offset stacking is ON or OFF. The net outcome of this electrostatic interaction between the neighbors is creation of new sequence-dependent hybrid nucleobases in an oligo- or polynucleotide whose properties are unlike the monomeric counterpart, which may have considerable biological implications.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-91150 (URN)10.1021/ja034651h (DOI)12914458 (PubMedID)
    Available from: 2003-11-26 Created: 2003-11-26 Last updated: 2017-12-14Bibliographically approved
    7. Significant pKa Perturbation of Nucleobases Is an Intrinsic Property of the Sequence Context in DNA and RNA
    Open this publication in new window or tab >>Significant pKa Perturbation of Nucleobases Is an Intrinsic Property of the Sequence Context in DNA and RNA
    Show others...
    2004 In: J. Am. Chem. Soc., Vol. 126, p. 8674-8681Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94246 (URN)
    Available from: 2006-04-07 Created: 2006-04-07Bibliographically approved
    8. Single-Stranded Adenine-Rich DNA and RNA Retain Structural Characteristics of Their Respective Double-Stranded Conformations and Show Directional Differences in Stacking Pattern
    Open this publication in new window or tab >>Single-Stranded Adenine-Rich DNA and RNA Retain Structural Characteristics of Their Respective Double-Stranded Conformations and Show Directional Differences in Stacking Pattern
    Show others...
    2004 In: Biochemistry, Vol. 43, p. 15996-16010Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94247 (URN)
    Available from: 2006-04-07 Created: 2006-04-07Bibliographically approved
    9. Measurement of Nucleobase pKa Values in Model Mononucleotides Shows RNA-RNA Duplexes To Be More Stable than DNA-DNA Duplexes
    Open this publication in new window or tab >>Measurement of Nucleobase pKa Values in Model Mononucleotides Shows RNA-RNA Duplexes To Be More Stable than DNA-DNA Duplexes
    Show others...
    2004 In: J. Am. Chem. Soc., Vol. 126, p. 2862-2869Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94248 (URN)
    Available from: 2006-04-07 Created: 2006-04-07Bibliographically approved
  • 22. Acharya, Sandipta
    et al.
    Barman, Jharna
    Cheruku, Pradeep
    Chatterjee, Subhrangsu
    Acharya, Parag
    Isaksson, Johan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, Jyoti
    Significant pKa Perturbation of Nucleobases Is an Intrinsic Property of the Sequence Context in DNA and RNA2004In: J. Am. Chem. Soc., ISSN 0002-7863, Vol. 126, p. 8674-8681Article in journal (Refereed)
  • 23.
    Acharya, Sandipta
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Barman, Jharna
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Cheruku, Pradeep
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chatterjee, Subhrangsu
    Acharya, Parag
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Isaksson, Johan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, Jyoti
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Significant pKa perturbation of nucleobases is an intrinsic property of the sequence context in DNA and RNA.2004In: J Am Chem Soc, ISSN 0002-7863, Vol. 126, no 28, p. 8674-81Article in journal (Other scientific)
  • 24.
    Acharya, Sandipta
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Barman, Jharna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Cheruku, Pradeep
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chatterjee, Subhrangsu
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, Parag
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Isaksson, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, Jyoti
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Significant pKa Perturbation of Nucleobases Is an Intrinsic Property of the Sequence Context in DNA and RNA2004In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 126, no 28, p. 8674-8681Article in journal (Refereed)
  • 25.
    Amirkhanov, N V
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    The RNase H Affinity and Cleavage of the target RNA in the Antisense-RNA Hybrid Duplexes Containing various 3’-Tethered Substituents in the Antisense Strand.2002In: J. Chem. Soc. Perkin 2, Vol. 2, p. 271-281Article in journal (Refereed)
  • 26.
    Amirkhanov, N V
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Pradeepkumar, P I
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Kinetic Analysis of the RNA Cleavage of the oxetane modified Antisense-RNA Hybrid Duplex by RNase H.2002In: J. Chem. Soc. Perkin 2, Vol. 5, p. 976-984Article in journal (Refereed)
  • 27.
    Amirkhanov, NV
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Zamaratski, E
    Chattopadhyaya, J
    The recognition and cleavage of RNA in the antisense oligo-RNA hybrid duplexes by RNase H2001In: TETRAHEDRON LETTERS, ISSN 0040-4039, Vol. 42, no 3, p. 489-491Article in journal (Refereed)
    Abstract [en]

    The different extent of the target RNA cleavage at t(99.9%) by RNase H in the AON-RNA duplexes, at the RNA saturation condition by antisense oligo, is due to different recognition and catalytic properties of RNase H toward the hybrids owing to different s

  • 28. Barman, J.
    et al.
    Acharya, S.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chuanzheng, Z.
    Chatterjee, S.
    Engström, A.
    Chattopadhyaya, J.
    Non-identical electronic characters of the internucleotidic pohosphates in RNA modulate the chemical reactivity of the phosphodiester bonds2006In: Org. Biomol. Chem., Vol. 4, p. 928-941Article in journal (Refereed)
  • 29.
    Barman, Jharna
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry. Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Acharya, Sandipta
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry. Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Zhou, Chuanzheng
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry. Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Chatterjee, Subhrangsu
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry. Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Engström, Åke
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Chattopadhyaya, Jyoti
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry. Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Non-identical electronic characters of the internucleotidic phosphates in RNA modulate the chemical reactivity of the phosphodiester bonds.2006In: Org Biomol Chem, ISSN 1477-0520, Vol. 4, no 5, p. 928-41Article in journal (Refereed)
  • 30.
    Barman, Jharna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, Sandipta
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Zhou, Chuanzheng
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chatterjee, Subhrangsu
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Engström, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Chattopadhyaya, Jyoti
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Non-identical electronic characters of the internucleotidic phosphates in RNA modulate the chemical reactivity of the phosphodiester bonds2006In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 4, no 5, p. 928-941Article in journal (Refereed)
    Abstract [en]

    We here show that the electronic properties and the chemical reactivities of the internucleotidic phosphates in the heptameric ssRNAs are dissimilar in a sequence-specific manner because of their non-identical microenvironments, in contrast with the corresponding isosequential ssDNAs. This has been evidenced by monitoring the delta H8(G) shifts upon pH-dependent ionization (pK(a1)) of the central 9-guaninyl (G) to the 9-guanylate ion (G(-)), and its electrostatic effect on each of the internucleotidic phosphate anions, as measured from the resultant delta P-31 shifts (pKa(2)) in the isosequential heptameric ssRNAs vis-`a-vis ssDNAs: [d/r( 5'-Cp(1)Ap(2)Q(1)p(3)Gp(4)Q(2)p(5)Ap(6)C-3'): Q(1) = Q(2) = A (5a/5b) or C (8a/8b), Q(1) = A, Q(2) = C (6a/6b), Q(1) = C, Q(2) = A (7a/7b)]. These oligos with single ionizable G in the centre are chosen because of the fact that the pseudoaromatic character of G can be easily modulated in a pH-dependent manner by its transformation to G(-) (the 2'-OH to 2-O- ionization effect is not detectable below pH 11.6 as evident from the N1-Me-G analog), thereby modulating/titrating the nature of the electrostatic interactions of G to G- with the phosphates, which therefore constitute simple models to interrogate how the variable pseudoaromatic characters of nucleobases under different sequence context (J. Am. Chem. Soc., 2004, 126, 8674-8681) can actually influence the reactivity of the internucleotide phosphates as a result of modulation of sequence context-specific electrostatic interactions. In order to better understand the impact of the electrostatic effect of the G to G- on the tunability of the electronic character of internucleotidic phosphates in the heptameric ssRNAs 5b, 6b, 7b and 8b, we have also performed their alkaline hydrolysis at pH 12.5 at 20 degrees C, and have identified the preferences of the cleavage sites at various phosphates, which are p(2), p(3) and p(4) (Fig. 3). The results of these alkaline hydrolysis studies have been compared with the hydrolysis of analogous N1-Me-G heptameric ssRNA sequences 5c, 7c and 8c under identical conditions in order to establish the role of the electrostatic effect of the 9-guanylate ion (and the 2'-OH to 2-O- ionization) on the internucleotidic phosphate. It turned out that the relative alkaline hydrolysis rate at those particular phosphates ( p2, p3 and p(4)) in the N1-Me-G heptamers was reduced from 16-78% compared to those in the native counterparts [Fig. 4, and ESI 2 (Fig. S11)]. Thus, these physico-chemical studies have shown that those p2, p3 and p4 phosphates in the native heptameric RNAs, which show pK(a2) as well as more deshielding ( owing to weaker P-31 screening) in the alkaline pH compared to those at the neutral pH, are more prone to the alkaline hydrolysis because of their relatively enhanced electrophilic character resulting from weaker P-31 screening. This screening effect originates as a result of the systematic charge repulsion effect between the electron cloud in the outermost orbitals of phosphorus and the central guanylate ion, leading to delocalization of the phosphorus pp charge into its d pi orbitals. It is thus likely that, just as in the non-enzymatic hydrolysis, the enzymatic hydrolysis of a specific phosphate in RNA by general base-catalyss in RNA-cleaving proteins (RNase A, RNA phosphodiesterase or nuclease) can potentially be electrostatically influenced by tuning the transient charge on the nucleobase in the steric proximity or as a result of specific sequence context owing to nearest-neighbor interactions.

  • 31.
    Bogucka, M.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Tech