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  • 101.
    P, Acharya
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    S, Acharya
    A, Földesi
    J, Chattopadhyaya
    Tandem Electrostatic Effect From the First to the Third Aglycon in the Trimeric RNA Owing to the Nearest-neighbor Stacking2003In: J. Am. Chem. Soc., Vol. 125, no 8, p. 2094-2100Article in journal (Refereed)
  • 102.
    Plashkevych, O
    et al.
    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.
    Conformational analysis of antisense 2'-oxetane modified DNA/RNA duplexes as substrates for RNase H2002Report (Other academic)
  • 103.
    Plashkevych, Oleksandr
    et al.
    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.
    Honcharenko, Dmytro
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Pathmasiri, Wimal
    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.
    Chemical and Structural Implications of 1‘,2‘- versus 2‘,4‘- Conformational Constraints in the Sugar Moiety of Modified Thymine Nucleosides2007In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 72, no 13, p. 4716-4726Article in journal (Refereed)
    Abstract [en]

    In order to understand how the chemical nature of the conformational constraint of the sugar moiety in ON/RNA(DNA) dictates the duplex structure and reactivity, we have determined molecular structures and dynamics of the conformationally constrained 1‘,2‘-azetidine- and 1‘,2‘-oxetane-fused thymidines, as well as their 2‘,4‘-fused thymine (T) counterparts such as LNA-T, 2‘-amino LNA-T, ENA-T, and aza-ENA-T by NMR, ab initio (HF/6-31G** and B3LYP/6-31++G**), and molecular dynamics simulations (2 ns in the explicit aqueous medium). It has been found that, depending upon whether the modification leads to a bicyclic 1‘,2‘-fused or a tricyclic 2‘,4‘-fused system, they fall into two distinct categories characterized by their respective internal dynamics of the glycosidic and the backbone torsions as well as by characteristic North-East type sugar conformation (P = 37° ± 27°, φm = 25° ± 18°) of the 1‘,2‘-fused systems, and (ii) pure North type (P = 19° ± 8°, φm = 48° ± 4°) for the 2‘,4‘-fused nucleosides. Each group has different conformational hyperspace accessible, despite the overall similarity of the North-type conformational constraints imposed by the 1‘,2‘- or 2‘,4‘-linked modification. The comparison of pKas of the 1-thyminyl aglycon as well as that of endocyclic sugar-nitrogen obtained by theoretical and experimental measurements showed that the nature of the sugar conformational constraints steer the physicochemical property (pKa) of the constituent 1-thyminyl moiety, which in turn can play a part in tuning the strength of hydrogen bonding in the basepairing.

  • 104.
    Pradeepkumar, PI
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    Oxetane modified antisense oligonucleotides promote RNase H cleavage of the complementary RNA strand in the hybrid duplex as efficiently as the native, and offer improved endonuclease resistance2001In: JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, ISSN 1472-779X, no 11, p. 2074-2083Article in journal (Refereed)
    Abstract [en]

    Although the T-m drops similar to6 degreesC/modification (note: T-m loss is similar to 10 degreesC/mismatch) in the oxetane, [1-(1',3'-O-anhydro-beta -D-psicofuranosyl)thymine, (T) under bar], modified antisense (AON)-RNA heteroduplexes, the relative rate

  • 105.
    Pradeepkumar, PI
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Zamaratski, E
    Foldesi, A
    Chattopadhyaya, J
    Conformation-specific cleavage of antisense oligonucleotide-RNA duplexes by RNase H2001In: JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, ISSN 1472-779X, no 3, p. 402-408Article in journal (Refereed)
    Abstract [en]

    The North-form (3'-endo) constrained 1-(1',3'-O-anhydro-beta -D-psicofuranosyl)thymine block, T, was systematically incorporated at various sites, one at a time, into a set of four antisense oligonucleotides (AONs). The hybrids of these AONs with a matche

  • 106.
    Pradeepkumar, PI
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Zamaratski, E
    Foldesi, A
    Chattopadhyaya, J
    Transmission of the conformational information in the antisense/RNA hybrid duplex influences the pattern of the RNase H cleavage reaction2000In: TETRAHEDRON LETTERS, ISSN 0040-4039, Vol. 41, no 44, p. 8601-8607Article in journal (Refereed)
    Abstract [en]

    A set of four hybrid duplexes formed by antisense oligos, each containing one North-form (3'-endo) locked 1-(1',3'-O-anhydro-beta -D-psicofuranosyl) thymine block T at different sites and a matched 15mer RNA, were subjected to the RNase H cleavage reactio

  • 107.
    Pradeepkumar, Pushpangadan I
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Amirkhanov, Nariman V
    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.
    Antisense oligonuclotides with oxetane-constrained cytidine enhance heteroduplex stability, and elicit satisfactory RNase H response as well as showing improved resistance to both exo and endonucleases.2003In: Org Biomol Chem, ISSN 1477-0520, Vol. 1, no 1, p. 81-92Article in journal (Other scientific)
  • 108.
    Pradeepkumar, Pushpangadan I
    et al.
    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.
    Plashkevych, Oleksandr
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, Parag
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Gohil, Suresh
    Chattopadhyaya, Jyoti
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Synthesis, physicochemical and biochemical studies of 1',2'-oxetane constrained adenosine and guanosine modified oligonucleotides, and their comparison with those of the corresponding cytidine and thymidine analogues.2004In: J Am Chem Soc, ISSN 0002-7863, Vol. 126, no 37, p. 11484-99Article in journal (Other scientific)
  • 109.
    Pradeepkumar, Pushpangadan Indira
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chemically Modified Oligonucleotides: Synthesis, Physicochemical and Biochemical Properties of their Duplexes with DNA and RNA2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is based on 9 papers dealing with the synthesis, physicochemical and biochemical properties of two types of chemically modified oligonucleotides which have the potential to down-regulate gene expression: (i) The first set is comprised of antisense oligonucleotides (AONs) conjugated with different chromophores of varying size, charge and π-electron density. Conjugation of the chromophores at the 3'- or 5'-end enhanced the target RNA binding affinity and RNase H recruitment capabilities compared to the native counterpart without changing the global helical conformation of their AON/RNA hybrid duplexes. The 3'-dipyridophenazine (DPPZ) has emerged as the most promising non-toxic chromophore in this series. (ii) The second set encompasses a new class of AONs containing North-East conformationally constrained 1',2'-oxetane-nucleosides. The introduction of oxetane-T and -C units imparts lowering of the Tm by ~ 6º and ~ 3 ºC/modification, respectively, of the AON/RNA hybrids, whereas the incorporation of the corresponding oxetane-A and-G units into AONs did not alter the thermostability in comparison with that of the native hybrid duplex. The oxetane-modified AONs have been found to possess enhanced serum stability compared to that of the native, whereas oxetane-T and -C containing AONs were more endonuclease-resistant than oxetane-A and-G modified AONs. All oxetane-modified mixmer AON/ RNA hybrid duplexes were, however, found to be excellent substrates for RNase H cleavage, which has been analyzed by Michaelis-Menten kinetics. The oxetane-modified mixmer AONs have shown effective down-regulation of the proto-oncogene c-myb mRNA in the K562 human leukemia cells, which was analyzed by QRT-PCR and Western Blot. Based on the amount of AON uptake after delivery, determined by slot blot, it was apparent that the oxetane-modified AONs are 5-6 times more effective antisense agents than the corresponding isosequential phosphorothioate analogues. The electrochemical assay based on sensitive nucleic acid mediated charge transport (CT) has revealed that the presence of oxetane-T unit causes more stacking perturbations in a DNA/DNA duplex than in a DNA/RNA duplex.

    List of papers
    1. The 3'-modified antisense oligos promote faster hydrolysis of the target RNA by RNase H than the natural counterpart
    Open this publication in new window or tab >>The 3'-modified antisense oligos promote faster hydrolysis of the target RNA by RNase H than the natural counterpart
    Show others...
    2001 In: Tetrahedron, Vol. 57, p. 593-606Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91705 (URN)
    Available from: 2004-04-26 Created: 2004-04-26Bibliographically approved
    2. Transmission of the conformational information in the antisense/RNA hybrid duplex influences the pattern of the RNase H cleavage reaction
    Open this publication in new window or tab >>Transmission of the conformational information in the antisense/RNA hybrid duplex influences the pattern of the RNase H cleavage reaction
    2000 In: Tetrahedron Letters, Vol. 41, p. 8601-8607Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91706 (URN)
    Available from: 2004-04-26 Created: 2004-04-26Bibliographically approved
    3. Conformation-specific cleavage of antisense oligonucleotide-RNA duplexes by RNase H
    Open this publication in new window or tab >>Conformation-specific cleavage of antisense oligonucleotide-RNA duplexes by RNase H
    2001 In: Journal of Chemical Society, Perkin Transactions 2, p. 402-408Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91707 (URN)
    Available from: 2004-04-26 Created: 2004-04-26Bibliographically approved
    4. Oxetane modified antisense oligonucleotides promote RNase H cleavage of the complementary RNA strand in the hybrid duplex as efficiently as the native, and offer improved endonuclease resistance
    Open this publication in new window or tab >>Oxetane modified antisense oligonucleotides promote RNase H cleavage of the complementary RNA strand in the hybrid duplex as efficiently as the native, and offer improved endonuclease resistance
    2001 In: Journal of Chemical Society, Perkin Transactions 2, p. 2074-2083Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91708 (URN)
    Available from: 2004-04-26 Created: 2004-04-26Bibliographically approved
    5. Antisense oligonucleotides with oxetane-constrained cytidine enhance heteroduplex stability, elicit satisfactory RNase H response as well as show improved resistance to both exo and endonucleases
    Open this publication in new window or tab >>Antisense oligonucleotides with oxetane-constrained cytidine enhance heteroduplex stability, elicit satisfactory RNase H response as well as show improved resistance to both exo and endonucleases
    2003 In: Organic and Biomolecular Chemistry, Vol. 1, p. 81-92Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91709 (URN)
    Available from: 2004-04-26 Created: 2004-04-26Bibliographically approved
    6. Synthesis, physicochemical and biochemical studies of 1',2'-oxetane constrained adenosine and guanosine modified oligonucleotides, and their comparison with those of the corresponding cytidine and thymidine analogs
    Open this publication in new window or tab >>Synthesis, physicochemical and biochemical studies of 1',2'-oxetane constrained adenosine and guanosine modified oligonucleotides, and their comparison with those of the corresponding cytidine and thymidine analogs
    Show others...
    In: Journal of American Chemical SocietyArticle in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-91710 (URN)
    Available from: 2004-04-26 Created: 2004-04-26 Last updated: 2015-05-19Bibliographically approved
    7. Rationally targeted, conformationally-constrained, oxetane modified oligonucleotides are highly efficient gene silencing molecules
    Open this publication in new window or tab >>Rationally targeted, conformationally-constrained, oxetane modified oligonucleotides are highly efficient gene silencing molecules
    Show others...
    In: Proceedings of National Academy of Sciences, USAArticle in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-91711 (URN)
    Available from: 2004-04-26 Created: 2004-04-26Bibliographically approved
    8. Synthesis of [Ru(phen)2dppz]2+-tethered oligo DNA and studies on the metallointercalation mode into the DNA duplex
    Open this publication in new window or tab >>Synthesis of [Ru(phen)2dppz]2+-tethered oligo DNA and studies on the metallointercalation mode into the DNA duplex
    2001 In: Journal of American Chemical Society, Vol. 123, p. 3551-3562Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91712 (URN)
    Available from: 2004-04-26 Created: 2004-04-26Bibliographically approved
    9. An electrochemical probe of DNA stacking in an antisense oligonucleotide containing C3'-endo locked sugar
    Open this publication in new window or tab >>An electrochemical probe of DNA stacking in an antisense oligonucleotide containing C3'-endo locked sugar
    Show others...
    2002 In: Angewandte Chemie International Edition, Vol. 41, p. 3402-3405Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91713 (URN)
    Available from: 2004-04-26 Created: 2004-04-26Bibliographically approved
  • 110.
    Pradeepkumar, Pushpangadan Indira
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Amirkhanov, Nariman
    Chattopadhyaya, Jyoti
    Antisense oligonucleotides with oxetane-constrained cytidine enhance heteroduplex stability, elicit satisfactory RNase H response as well as show improved resistance to both exo and endonucleases2003In: Organic and Biomolecular Chemistry, Vol. 1, p. 81-92Article in journal (Refereed)
  • 111.
    Pradeepkumar, Pushpangadan Indira
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, Jyoti
    Oxetane modified antisense oligonucleotides promote RNase H cleavage of the complementary RNA strand in the hybrid duplex as efficiently as the native, and offer improved endonuclease resistance2001In: Journal of Chemical Society, Perkin Transactions 2, p. 2074-2083Article in journal (Refereed)
  • 112.
    Pradeepkumar, Pushpangadan Indira
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Cheruku, Pradeep
    Plashkevych, Oleksandr
    Acharya, Parag
    Gohil, Suresh
    Chattopadhyaya, Jyoti
    Synthesis, physicochemical and biochemical studies of 1',2'-oxetane constrained adenosine and guanosine modified oligonucleotides, and their comparison with those of the corresponding cytidine and thymidine analogsIn: Journal of American Chemical SocietyArticle in journal (Refereed)
  • 113.
    Pradeepkumar, Pushpangadan Indira
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Zamaratski, Edouard
    Foldesi, Andras
    Chattopadhyaya, Jyoti
    Conformation-specific cleavage of antisense oligonucleotide-RNA duplexes by RNase H2001In: Journal of Chemical Society, Perkin Transactions 2, p. 402-408Article in journal (Refereed)
  • 114.
    Pradeepkumar, Pushpangadan Indira
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Zamaratski, Edouard
    Foldesi, Andras
    Chattopadhyaya, Jyoti
    Transmission of the conformational information in the antisense/RNA hybrid duplex influences the pattern of the RNase H cleavage reaction2000In: Tetrahedron Letters, Vol. 41, p. 8601-8607Article in journal (Refereed)
  • 115.
    Puri, N
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Chattopadhyaya, J
    Physico-chemical properties of 5 '-polyarene tethered DNA-conjugates, and their duplexes with complementary RNA1999In: NUCLEOSIDES & NUCLEOTIDES, ISSN 0732-8311, Vol. 18, no 11-12, p. 2785-2818Article in journal (Refereed)
    Abstract [en]

    Fluorophores 1-13 when covalently linked to the 5'-terminus of 9-mer ssDNA (as in ssDNA-conjugates 16-28) enhance the stablity of the duplexes with both RNA (29) and DNA (30) targets compared to the natural counterparts, which, for the first time, demonst

  • 116.
    Puri, Nitin
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Studies on nucleic acids chemistry1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is divided into three parts:

    Part 1: Synthesis and conformational analysis of cyclic RNAs, and comparison with lariat RNAs modelling the lariat formed during processing of Group II and Nuclear pre-mRNA. Synthesis of a hexameric lariat RNA model with a tetranucleotidyl "2' → 5' loop" and a dinucleotidyl "3'-tail" has been accomplished. The hexameric lariat and its heptameric analogue displayed unique self-cleavage giving products, mimicking those obtained in the self-cleavage reactions of catalytic RNA (ribozyme). To elucidate the role of the "3'-tail" in the observed self-cleavage, two cyclic tetrameric (2' → 5' at A1) and (3' → 5' at A1) RNAs were synthesized. A comparison of the conformations adopted by them and the hexameric lariat-RNA highlighted that just an ethyl phosphate as the "3'-tail" is adequate to engineer the local geometrical changes that are required for the self-cleavage reaction.

    Part 2: Synthesis and utility of cyclic phosphitylating agents in the one-pot synthesis of biologically relevant phosphorothioates. The synthesis of new aromatic cyclic five-membered P(III) phosphoramidite is reported. MAC activation of these phosphitylating reagents made it feasible to generate unsymmetrical trisubstituted phosphates by stepwise reacting the activated phosphole with three different nucleophiles. The use of the 5-chloro phosphole analog was demonstrated in the one-pot synthesis of various biological oligophosphates such as P1,Pn-(diadenosine 5')-polyphosphates, P1-(N-7-methylguanosine 5')-P3-(adenosine 5')-1-thiotriphosphate, nucleoside 5'-polyphosphates, nucleoside 2',3'-cyclic phosphorothioate, nucleoside phosphorothioates and trinucleoside monophosphate.

    Part 3: Synthesis and physicochemical studies on duplexes and triplexes of DNA-conjugates: A class of potential antisense and antigene agents. DNA-conjugates have found utility in antigene and antisense strategies as repressors of gene expression at the transcriptional and translational levels. The first synthesis of the C-branched spermine is herein reported. It was covalently linked through a phosphate linkage ontothe 5'-end of a ssDNA, and through the 2'-phosphate of the arabinose-Uracil to the medial and the 3'-end of ssDNA. The resulting DNA conjugates augmented the thermal stability of their duplexes and triplexes formed with ssDNA and dsDNA. Additionally, thirteen different planar hydroxy alkylated polyarenes with different geometries, bulk and π-electron densities were synthesized. Tethering them through a phosphate linkage to the 5'-terminus of ssDNA enabled us to demonstrate the influence of varying the electronic and bulk characteristics of these polyarenes on the thermal stability and fluorescence properties of the resulting hetero/homoduplexes and the triplexes. CD displayed no gross changes in the native hetero/homoduplex global structure on tethering these fluorophores. It has also emerged that these 5'-tethered fluorophores assist in pre-organization of DNA-conjugates owing to which they adopt a less random coil structure than their native counterparts. All heteroduplexes tested underwent RNA excision by RNase H. Finally, a significant hurdle in the antisense strategy, which is that of the kinetic inaccessibility of mRNA, is addressed using a small 20-mer RNA. This 20-mer RNA adopts a duplex structure which did not form a complex with our DNA-conjugates, while its DNA counterpart which formed a hairpin did.

  • 117.
    S, Acharya
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    P, Acharya
    A, Földesi
    J, Chattopadhyaya
    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, no 46, p. 13722-13730Article in journal (Refereed)
  • 118.
    Schjolden, Joachim
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Stress Coping Strategies in Rainbow Trout (Oncorhynchus mykiss)2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Animals show a great variety in physiological and behavioural responses to stressors. These responses are often bimodally distributed within populations and show consistency on an individual level over time and across situations, which in terrestrial vertebrates have been identified as proactive and reactive stress coping strategies. Proactive animals show lower cortisol responses, higher sympathetic activation and brain serotonergic activity compared to reactive animals. Behaviourally, proactive animals are more aggressive, more active in avoiding stressors, they form routines and show fewer cases of conditioned immobility compared to reactive animals. Our aim has been to reveal if such stress coping strategies exist in fish. Our results show that rainbow trout with high (HR) or low (LR) cortisol responses to stressors differs in sympathetic activation and brain serotonin turnover in the same manner as proactive and reactive mammals. HR fish showed less locomotor activity when reared in large groups (30 individuals) compared to LR fish. When reared in isolation there were no differences between HR and LR fish when exposed to stressors within a familiar environment. The adaption of a proactive coping style among reactive coping individuals when they are challenged within a familiar environment has previously been shown to be distinction between proactive and reactive coping mammals. However, when they were transferred to unfamiliar environments a behavioural difference between the two lines was observed indicating different stress coping strategies akin to those described in mammals. Finally, we observed a consistency over time in the cortisol response of an unselected line of rainbow trout. Fish from this line also demonstrated a correlation between behavioural responses to different stressors. However, there was no apparent connection between these behavioural responses and the cortisol response. Overall, the results of this thesis have strengthened the hypothesis that different stress coping strategies exist in teleost fish.

    List of papers
    1. Divergence in locomotor activity between two strains of rainbow trout Oncorhynchus mykiss with contrasting stress responsiveness
    Open this publication in new window or tab >>Divergence in locomotor activity between two strains of rainbow trout Oncorhynchus mykiss with contrasting stress responsiveness
    2006 (English)In: Journal of Fish Biology, ISSN 0022-1112, E-ISSN 1095-8649, Vol. 68, no 3, p. 920-924Article in journal (Other (popular science, discussion, etc.)) Published
    Abstract [en]

    Individuals of rainbow trout Oncorhynchus mykiss with a low cortisol response to stress showed higer locomotor activity compared to individuals with a high cortisol response.

    Keywords
    aggression, behaviour, coping styles, cortisol, salmonids, social interaction
    National Category
    Zoology
    Identifiers
    urn:nbn:se:uu:diva-21170 (URN)10.1111/j.0022-1112.2006.00935.x (DOI)
    Available from: 2006-12-15 Created: 2006-12-15 Last updated: 2017-12-08Bibliographically approved
    2. Divergence in behavioural responses to stress in two strains of rainbow trout (Oncorhynchus mykiss) with contrasting stress responsiveness
    Open this publication in new window or tab >>Divergence in behavioural responses to stress in two strains of rainbow trout (Oncorhynchus mykiss) with contrasting stress responsiveness
    Show others...
    2005 (English)In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 48, no 5, p. 537-544Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to establish whether two lines of rainbow trout divergent for their plasma cortisol response to a standardized stressor would show consistent differences in their behavioural response to a range of challenging situations. Our results show that the high- and low-responding (HR and LR) lines of rainbow trout did not differ in the aggression shown towards an intruder or in their response to the introduction of a novel object to their home environment. However, there was a difference in behaviour between the two selection lines when they were exposed to two unfamiliar environments. These results suggest that the behaviour of the HR and LR fish differs when they are challenged in unfamiliar environments, while their behaviour does not differ when they are challenged in their home environment. These observations are in agreement with studies on mammals that show that individuals with reactive coping styles perform similarly to proactive animals when they are challenged in a familiar environment, while they show different behaviour when they are challenged in unfamiliar environments. Thus, these results provide further evidence that the HR and LR selection lines of rainbow trout exemplify the two different coping styles described in mammals.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-93738 (URN)10.1016/j.yhbeh.2005.04.008 (DOI)
    Available from: 2005-11-22 Created: 2005-11-22 Last updated: 2017-12-14Bibliographically approved
    3. Serotonergic characteristics of rainbow trout divergent in stress responsiveness
    Open this publication in new window or tab >>Serotonergic characteristics of rainbow trout divergent in stress responsiveness
    Show others...
    In: Physiology and BehaviorArticle in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-93739 (URN)
    Available from: 2005-11-22 Created: 2005-11-22Bibliographically approved
    4. Does intraspecific variation in stress responses and agonistic behaviour reflect divergent stress coping strategies in juvenile rainbow trout?
    Open this publication in new window or tab >>Does intraspecific variation in stress responses and agonistic behaviour reflect divergent stress coping strategies in juvenile rainbow trout?
    2005 In: Physiological and Biochemical Zoology, ISSN 1522-2152, Vol. 78, no 5, p. 715-723Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-93740 (URN)
    Available from: 2005-11-22 Created: 2005-11-22Bibliographically approved
  • 119.
    Schjolden, Joachim
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Pulman, Kim G.T.
    Pottinger, Tom G.
    Tottmar, Olof
    Winberg, Svante
    Serotonergic characteristics of rainbow trout divergent in stress responsivenessIn: Physiology and BehaviorArticle in journal (Refereed)
  • 120.
    Schjolden, Joachim
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Stoskhus, Argaudas
    Winberg, Svante
    Does intraspecific variation in stress responses and agonistic behaviour reflect divergent stress coping strategies in juvenile rainbow trout?2005In: Physiological and Biochemical Zoology, ISSN 1522-2152, Vol. 78, no 5, p. 715-723Article in journal (Refereed)
  • 121.
    Srivastava, Puneet
    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.
    Pathmasiri, Wimal
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Plashkevych, Oleksandr
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Wenska, Małgorzata
    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.
    Five- and Six-Membered Conformationally Locked 2‘,4‘-Carbocyclic ribo-Thymidines: Synthesis, Structure, and Biochemical Studies2007In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 129, no 26, p. 8362-8379Article in journal (Refereed)
    Abstract [en]

    Two unusual reactions involving the 5-hexenyl or the 6-heptenyl radical cyclization of a distant double bond at C4' and the radical center at C2' of the ribofuranose ring of thymidine have been used as key steps to synthesize North-type conformationally constrained cis-fused bicyclic five-membered and six-membered carbocyclic analogues of LNA (carbocyclic-LNA-T) and ENA (carbocyclic-ENA-T) in high yields. Their structures have been confirmed unambiguously by long range iH-13C NMR correlation (HMBC), TOCSY, COSY, and NOE experiments. The carbocyclic-LNA-T and carbocyclic-ENA-T were subsequently incorporated into the antisense oligonucleotides (AONs) to show that they enhance the Tm of the modified AON/RNA heteroduplexes by 3.5-5 °C and 1.5 °C/modification for carbocyclic-LNA-T and carbocyclic-ENA-T, respectively. Whereas the relative RNase H cleavage rates with carbocyclic-LNA-T, carbocyclic-ENA-T, aza-ENA-T, and LNA-T modified AON/RNA duplexes were found to be very similar to that of the native counterpart, irrespective of the type and the site modification in the AON strand, a single incorporation of carbocyclic-LNA and carbocyclic-ENA into AONs leads to very much more enhanced nuclease stability in the blood serum (stable >48 h) as compared to that of the native (fully degraded <3 h) and the LNA-modified AONs (fully degraded <9 h) and aza-ENA (≈85% stable in 48 h). Clearly, remarkably enhanced lifetimes of these carbocyclic-modified AONs in the blood serum may produce the highly desired pharmacokinetic properties because of their unique stability and consequently a net reduction of the required dosage. This unique quality as well as their efficient use as the AON in the RNase H-promoted cleavage of the target RNA makes our carbocyclic-LNA and carbocyclic-ENA modifications excellent candidates as potential antisense therapeutic agents.

  • 122.
    Thibaudeau, Christophe
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Stereoelectronic effects in nucleosides and nucleotides1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is based on 12 original publications from 1994-98. Intramolecular stereoelectronicforces (anomeric and gauche effects), beside intermolecular forces such as hydrogen bonding,base stacking, electrostatics and hydration, have been found to be responsible for the localstructural changes of DNA and RNA and their components. A detailed insight into the stereoelectronic forces has been obtained by a systematic pairwise comparison of the thermodynamics in various N- and C-nucleosides at several pDs, determined from pseudorotational analyses of 3JHH. This has allowed us to understand how the electronic character of various sugar substituents modulates the strengths of the stereoelectronic drive of the sugar conformation. Evidences have been put forward supporting that both the anomeric and gauche effects result from the appropriate orbital mixing rather than dipole-dipole interactions: the nucleobase-dependent anomeric effect results nO4'→Σ* C1'-N1/9 interaction, whereas the gauche effect originates from Σ→Σ* orbital mixing. It has been demonstrated that the modulations of the gauche and the anomeric effect are interrelated, and mutually influence each other, and the final outcome of the free-energy of the sugar conformational equilibrium is a result of this enthalpic interplay and of the entropy. The electronic character of the nucleobase at various pDs is transmitted to steer the sugar conformation in β-nucleosides owing to the modulation of the anomeric and gauche effects. The strength of the anomeric effect in α-nucleosides is reduced compared to β-counterparts owing to weaker overlap of O4' lonepairs with Σ* C1'N1/9. In C-nucleosides, the conformation of the sugar moiety is dictated by nO4' →Σ* C1'C5/9(sp2) interactions, which are reduced and enhanced at acidic and alkaline pDs. The strength of the nO4'→Σ* C1'-N1/9 anomeric effect in adenosine and guanosine and in their 2'-deoxy counterparts has been quantitated using 9-deazaadenosine as a reference point for the estimation of the counteracting steric effect of the nucleobase in the N-nucleosides. The interaction of 2'-OH with the vicinal phosphate results in a unique two-state (N,εt ) ↔ (S,ε-) equilibrium in 3'- ethylphosphate ribonucleotides whereas in 2'-deoxy counterparts no correlation between sugar and phosphate-backbone conformation could be detected.

    A quantitative Karplus-type equation for the translation of 3JHF into ΦHCCF has beenparametrized for the first time, taking into account effects of orientation and electronegativity of substituents and the influence of HCC and FCC bond angle changes. The application of this equation to pseudorotational analyses of 3JHF in combination with 3JHH has allowed to quantitatively describe the conformation of several antiviral and antitumour mono and difluoronucleosides.

  • 123. Usova, Elena
    et al.
    Maltseva, Tatiana
    Földesi, Andras
    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.
    Eriksson, Staffan
    Human deoxycytidine kinase as a deoxyribonucleoside phosphorylase.2004In: J Mol Biol, ISSN 0022-2836, Vol. 344, no 5, p. 1347-58Article in journal (Other scientific)
  • 124.
    Varghese, Oommen P.
    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.
    Pathmasiri, Wimal
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Plashkevych, Oleksandr
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Honcharenko, Dmytro
    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.
    Conformationally constrained 2'-N,4'-C-ethylene-bridged thymidine (aza-ENA-T): synthesis, structure, physical, and biochemical studies of aza-ENA-T-modified oligonucleotides2006In: J. Am. Chem. Soc., Vol. 128, no 47, p. 15173-15187Article in journal (Refereed)
  • 125.
    Varghese, Oommen P.
    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.
    Pathmasiri, Wimal
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Plashkevych, Oleksandr
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Honcharenko, Dmytro
    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.
    Conformationally Constrained 2'-N,4'-C-Ethylene-Bridged Thymidine (Aza-ENA-T): Synthesis, Structure, Physical, and Biochemical Studies of Aza-ENA-T-Modified Oligonucleotides2006In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 128, no 47, p. 15173-15187Article in journal (Refereed)
    Abstract [en]

    The 2'-deoxy-2'-N,4'-C-ethylene-bridged thymidine (aza-ENA-T) has been synthesized using a key cyclization step involving 2'-ara-trifluoromethylsufonyl-4'-cyanomethylene 11 to give a pair of 3',5'-bis-OBn- protected diastereomerically pure aza-ENA-Ts (12a and 12b) with the fused piperidino skeleton in the chair conformation, whereas the pentofuranosyl moiety is locked in the North-type conformation (7 < P < 27 degrees, 44 degrees < phi(m) < 52 degrees). The origin of the chirality of two diastereomerically pure aza-ENA-Ts was found to be due to the endocyclic chiral 2'-nitrogen, which has axial N-H in 12b and equatorial N-H in 12a. The latter is thermodynamically preferred, while the former is kinetically preferred with E-a 25.4 kcal mol(-1), which is thus far the highest observed inversion barrier at pyramidal N-H in the bicyclic amines. The 5'-O-DMTr-aza-ENA-T-3'-phosphoramidite was employed for solid-phase synthesis to give four different singly modified 15-mer antisense oligonucleotides (AONs). Their AON/RNA duplexes showed a T m increase of 2.5-4 degrees C per modification, depending upon the modification site in the AON. The relative rates of the RNase H1 cleavage of the aza-ENA-T-modified AON/RNA heteroduplexes were very comparable to that of the native counterpart, but the RNA cleavage sites of the modified AON/RNA were found to be very different. The aza-ENA-T modifications also made the AONs very resistant to 3' degradation (stable over 48 h) in the blood serum compared to the unmodified AON (fully degraded in 4 h). Thus, the aza-ENA-T modification in the AON fulfilled three important antisense criteria, compared to the native: (i) improved RNA target affinity, (ii) comparable RNase H cleavage rate, and (iii) higher blood serum stability.

  • 126.
    Velikian, I
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, P
    Trifonova, A
    Foldesi, A
    Chattopadhyaya, J
    The RNA molecular wire: the pH-dependent change of the electronic character of adenin-9-yl is transmitted to drive the sugar and phosphate torsions in adenosine 3 ',5 '-bisphosphate2000In: JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, ISSN 0894-3230, Vol. 13, no 5, p. 300-305Article in journal (Refereed)
    Abstract [en]

    The change of the electronic character of adenin-9-yl in adenosine 3',5'-bisphosphate (EtpApMe, 1) in the neutral versus protonated form, in contrast to its abasic counterpart [Etp(apurinic)pMe, 2], is transmitted to modulate the sugar conformation by an

  • 127.
    Velikyan, I
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Acharya, S
    Trifonova, A
    Foldesi, A
    Chattopadhyaya, J
    The pK(a)'s of 2 '-hydroxyl group in nucleosides and nucleotides2001In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, ISSN 0002-7863, Vol. 123, no 12, p. 2893-2894Article in journal (Refereed)
  • 128. Velikyan, I.
    et al.
    Acharya, S.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Trifonova, A.
    Földesi, A.
    Chattopadhyaya, J.
    The pKa’s of 2'-Hydroxyl Group in Nucleosides and Nucleotides2001In: J. Am. Chem. Soc., Vol. 123, p. 2893-2894Article in journal (Refereed)
  • 129.
    Wang, YN
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry. QUANTUM CHEMISTRY.
    Eriksson, LA
    Physics, Department of Physics.
    B3LYP studies of the formation of neutral tyrosyl radical Y-Z(center dot) and regeneration of neutral tyrosine Y-Z in PSII2001In: INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, ISSN 0020-7608, Vol. 83, no 3-4, p. 220-229Article in journal (Refereed)
    Abstract [en]

    Tyrosine Y161 (Y-Z) plays an important role in the charge separation of photosystem II (PSII) by reducing photooxidized P680(+) and thus forming a neutral tyrosyl radical. The neutral tyrosyl radical then abstracts an electron and a proton from the mangan

  • 130.
    Zamaratski, E
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Ossipov, D
    Pradeepkumar, PI
    Amirkhanov, N
    Chattopadhyaya, J
    The 3 '-modified antisense oligos promote faster hydrolysis of the target RNA by RNase H than the natural counterpart2001In: TETRAHEDRON, ISSN 0040-4020, Vol. 57, no 3, p. 593-606Article in journal (Refereed)
    Abstract [en]

    We have examined the antisense potency of the hybrid duplexes of fully-matched 3'-, 5' and interior-chromophore tethered antisense oligos (AON) and three target RNAs (11mer and two 17mers) against RNase H, and found them to be better substrates compared t

  • 131.
    Zamaratski, E
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Pradeepkumar, PI
    Chattopadhyaya, J
    A critical survey of the structure-function of the antisense oligo/RNA heteroduplex as substrate for RNase H2001In: JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS, Vol. 48, no 3, p. 189-208Article, book review (Other scientific)
    Abstract [en]

    The aim of this review is to draw a correlation between the structure of the DNA/RNA hybrid and its properties as a substrate for the RNase H, as well as to point the crucial structural requirements for the modified AONs to preserve their RNase H potency.

  • 132.
    Zamaratski, E
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Trifonova, A
    Acharya, P
    Isaksson, J
    Maltseva, T
    Chatttopadhayaya, J
    Do the 16 mer, 5 '-GUGGUCUGAUGAGGCC-3 ' and the 25 mer, 5 '-GGCCGAAACUCGUAAGAGUCACCAC-3 ', form a hammerhead ribozyme structure in physiological conditions? An NMR and UV thermodynamic study2001In: NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, ISSN 1525-7770, Vol. 20, no 4-7, p. 1219-1223Article in journal (Refereed)
    Abstract [en]

    In a wide range of salt concentrations, 10-30 mM phosphate buffer containing up to 0.5 M Li2SO4 and 300 mM NaCl, 7.5 mM Mg2+, pH 5.5-7.5, a mixture of the 16 mer and the 25 mer RNA strands does not form a hammerhead in any amount detectable by NMR at 600

  • 133.
    Zamaratski, Edouard
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Some Aspects of Nucleic Acids Chemistry2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is divided into two parts based on a total of 8 papers: Part 1: Synthesis, physicochemical and biochemical studies of chemically modified oligonucleotides and their duplexes and triplexes. Potency of the chromophore conjugated DNA oligonucleotides as antigene and antisense gene repressors was evaluated. The effect of geometry, bulk and ¥ð-electron density of a series of chromophores, tethered at the 5'-end of oligonucleotides, as well as the effect of the linker nature, length and the attachment site of the chromophore to the oligo were explored based on the stability of the duplexes and triplexes. A dramatic improvement in the triplex stability with ara-U linked phenazine oligo (potent antigene) was achieved (¥ÄTm = 16.5¢ª C). A number of selected phenazine and dipyridophenazine tethered antisense oligos (AONs) and their phosphorothioate analogues were shown to form the AON/RNA hybrid duplexes with enhanced thermal stability. CD experiments revealed that these duplexes have the global structure unaltered from that of the native counterpart. RNase H degradation studies on three RNA targets having different degrees of folded structures showed that tethering of phenazine and dipyridophenazine increases the hydrolysis rates (potent antisense) of the target RNA, and that chemical nature of the chromophore influences the RNase H cleavage pattern. Further investigation at the RNA saturated conditions revealed that 3'-tethered chromophores influence the substrate recognition, and the kinetics of the cleavage by RNase H. Conjugation of different chromophores, charged polyaromatic systems and metal complexes with polyaromatic ligands at different sites of the AON revealed that RNase H is very sensitive to any modifications in the middle region of the AON/RNA duplex. On the contrary, any modification at the 3'-end of the AON regardless of the bulk of the substituent or presence of positive charge can be easily tolerated by the enzyme. Sensitivity of the RNase H towards the local structural changes in the AON/RNA hybrid was probed with a number of AONs containing a single 1-(1',3'-O-anhydro-©¬-D-psicofuranosyl)thymine with locked 3'-endo sugar conformation at different sites of AON. RNase H degradation studies revealed that the local conformational changes brought by the constrained nucleoside, although invisible by CD, span in the hybrid as far as 5 nucleotides toward the 5'-end of the AONs (3'-end of RNA), showing the unique transmission of the structural distortion from a single modification site. The results also showed that the structural requirements for the substrate binding and substrate cleavage by RNase H appear to be different. Part 2: Preparation of biologically important isotope labelled oligo-RNAs for the NMR structure determination in solution. Synthesis of the non-uniformly 13C5 labelled 29mer HIV-1 TAR RNA was achieved by solid-phase synthesis using 13C5 labelled ribonucleosides from 13C6-D-glucose). Two hammerhead forming RNAs (16mer and 25mer) were synthesized according to the Uppsala NMR-window strategy, where the sugar residues of the nucleosides forming stem I, II and the loop of the stem III of the resulting hammerhead complex were deuterated. UV melting and high resolution NMR structural studies showed that the 16mer RNA under quasiphysiological condition folds to a very stable hairpin structure, which prevents formation of a hammerhead RNA with the 25mer, primarily owing to thermodynamic reasons.

  • 134. Zamaratski, Edouard
    et al.
    Ossipov, Dimitri
    Pradeepkumar, Pushpangadan Indira
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Amirkhanov, Nariman
    Chattopadhyaya, Jyoti
    The 3'-modified antisense oligos promote faster hydrolysis of the target RNA by RNase H than the natural counterpart2001In: Tetrahedron, Vol. 57, p. 593-606Article in journal (Refereed)
  • 135.
    Zhou, Chuanzheng
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Honcharenko, Dmytro
    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.
    2-(4-Tolylsulfonyl)ethoxymethyl (TEM)-a new 2'-OH protecting group for solid-supported RNA synthesis2007In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 5, no 2, p. 333-343Article in journal (Refereed)
    Abstract [en]

    The 2-(4-tolylsulfonyl) ethoxymethyl (TEM) as a new 2'-OH protecting group is reported for solid-supported RNA synthesis using phosphoramidite chemistry. The usefulness of the 2'-O-TEM group is exemplified by the synthesis of 12 different oligo-RNAs of various sizes ( 14 - 38 nucleotides long). The stepwise coupling yield varied from 97 - 99% with an optimized coupling time of 120 s. The synthesis of all four pure phosphoramidite building blocks is also described. Two new reliable parameters, delta(C2') - delta(C3') and delta(H2') - delta(H3'), have been suggested for the characterization of isomeric 2'-O-TEM and 3'-O-TEM as well as other isomeric mono 2'/3'-protected ribonucleoside derivatives. The most striking feature of this strategy is that the crude RNA prepared using our 2'-O-TEM strategy is sufficiently pure (> 90%) for molecular biology research without any additional purification step, thereby making oligo-RNAs easily available at a relatively low cost, saving both time and lab resources.

  • 136.
    Zhou, Chuanzheng
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Pathmasiri, Wimal
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
    Honcharenko, Dmytro
    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.
    Barman, Jharna
    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.
    High-quality oligo-RNA synthesis using the new 2′-O-TEM protecting group by selectively quenching the addition of p-tolyl vinyl sulphone to exocyclic amino functions2007In: Canadian journal of chemistry (Print), ISSN 0008-4042, E-ISSN 1480-3291, Vol. 85, no 4, p. 293-301Article in journal (Refereed)
    Abstract [en]

    During the F--promoted deprotection of the oligo-RNA, synthesized using our 2′-O-(4-tolylsulfonyl)ethoxymethyl (2′-O-TEM) group [Org. Biomol. Chem. 5, 333 (2007)], p-tolyl vinyl sulphone (TVS) is formed as a by-product. The TVS formed has been shown to react with the exocyclic amino functions of adenosine (A), guanosine (G), and cytidine (C) of the fully deprotected oligo-RNA to give undesirable adducts, which are then purified by HPLC and unambiguously characterized by 1H, 13C Heteronuclear Multiple Bond Correlation (HMBC) NMR and mass spectroscopic analysis. The relative nucleophilic reactivities of the nucleobases toward TVS have been found to be the following: N6-A > N4-C > N2-G > > N3-U. This reactivity of TVS toward RNA nucleobases to give various Michael adducts could, however, be suppressed by using various amines as scavengers. Among all these amines, morpholine and piperidine are the most efficient scavenger for TVS, which gave highly pure oligo-RNA even in the crude form and can be used directly in RNA chemical biology studies.

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