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Yahorava, S
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Publications (8 of 8) Show all publications
Grigorjeva, L., Liepinsh, E., Razafimahefa, S., Yahorau, A., Yahorava, S., Rasoanaivo, P., . . . Wikberg, J. E. S. (2014). Semisynthesis of Libiguin A and Its Analogues by Trans-Lactonization of Phragmalin. Journal of Organic Chemistry, 79(9), 4148-4153
Open this publication in new window or tab >>Semisynthesis of Libiguin A and Its Analogues by Trans-Lactonization of Phragmalin
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2014 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 79, no 9, p. 4148-4153Article in journal (Refereed) Published
Abstract [en]

Libiguins are limonoids with highly potent sexual activity enhancing effects, originally isolated from the Madagascarian Meliaceae species Neobeguea mahafalensis, where they exist in only minute quantities. Their low natural abundance has hampered mapping of their biological effects. Here we describe an approach to the semisynthesis of libiguin A and its close analogues 1-3 starting from phragmalin, which is a limonoid present in high amounts in a commercially cultivated Meliaceae species, Chukrasia tabularis, allowing the preparation of libiguins in appreciable quantities.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-227184 (URN)10.1021/jo500318w (DOI)000335490700046 ()
Available from: 2014-06-26 Created: 2014-06-24 Last updated: 2017-12-05Bibliographically approved
Prusis, P., Junaid, M., Petrovska, R., Yahorava, S., Yahorau, A., Katzenmeier, G., . . . Wikberg, J. E. S. (2013). Design and evaluation of substrate-based octapeptide and non substrate-based tetrapeptide inhibitors of dengue virus NS2B-NS3 proteases. Biochemical and Biophysical Research Communications - BBRC, 434(4), 767-772
Open this publication in new window or tab >>Design and evaluation of substrate-based octapeptide and non substrate-based tetrapeptide inhibitors of dengue virus NS2B-NS3 proteases
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2013 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 434, no 4, p. 767-772Article in journal (Refereed) Published
Abstract [en]

A series of 45 peptide inhibitors was designed, synthesized, and evaluated against the NS2B-NS3 proteases of the four subtypes of dengue virus, DEN-1-4. The design was based on proteochemometric models for Michaelis (K-m) and cleavage rate constants (k(cat)) of protease substrates. This led first to octapeptides showing submicromolar or low micromolar inhibitory activities on the four proteases. Stepwise removal of cationic substrate non-prime side residues and variations in the prime side sequence resulted finally in an uncharged tetrapeptide, WYCW-NH2, with inhibitory K-i values of 4.2, 4.8, 24.4, and 11.2 mu M for the DEN-1-4 proteases, respectively. Analysis of the inhibition data by proteochemometric modeling suggested the possibility for different binding poses of the shortened peptides compared to the octapeptides, which was supported by results of docking of WYCW-NH2 into the X-ray structure of DEN-3 protease.

Keywords
Dengue virus, NS2B-NS3 protease, D-optimal design, Substrate-based, Non-substrate-based, Tetrapeptide inhibitor
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-203557 (URN)10.1016/j.bbrc.2013.03.139 (DOI)000320213200012 ()
Available from: 2013-07-15 Created: 2013-07-15 Last updated: 2017-12-06Bibliographically approved
Fossen, T., Rasoanaivo, P., Manjovelo, C. S., Raharinjato, F. H., Yahorava, S., Yahorau, A. & Wikberg, J. (2012). A new protolimonoid from Capuronianthus mahafalensis. Fitoterapia (Milano), 83(5), 901-906
Open this publication in new window or tab >>A new protolimonoid from Capuronianthus mahafalensis
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2012 (English)In: Fitoterapia (Milano), ISSN 0367-326X, E-ISSN 1873-6971, Vol. 83, no 5, p. 901-906Article in journal (Refereed) Published
Abstract [en]

From stem barks of Capuronianthus mahafalensis (Meliaceae) endemic to Madagascar, a new protolimonoid named capulin containing a four membered ring in its side chain was isolated by repeated silica gel column chromatography. Its structure was determined by 1D and 2D NMR spectroscopy and high-resolution MS. To the best of our knowledge, this is the first time that a four-membered ring occurs in the side chain of protolimonoids. 

Keywords
Capuronianthus mahafalensis, Protolimonoid, Capulin
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-177851 (URN)10.1016/j.fitote.2012.03.023 (DOI)000305657900014 ()
Available from: 2012-07-20 Created: 2012-07-19 Last updated: 2017-12-07Bibliographically approved
Prusis, P., Lapins, M., Yahorava, S., Petrovska, R., Niyomrattanakit, P., Katzenmeier, G. & Wikberg, J. E. (2008). Proteochemometrics analysis of substrate interactions with dengue virus NS3 proteases. Bioorganic & Medicinal Chemistry, 16(20), 9369-9377
Open this publication in new window or tab >>Proteochemometrics analysis of substrate interactions with dengue virus NS3 proteases
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2008 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 16, no 20, p. 9369-9377Article in journal (Refereed) Published
Abstract [en]

The prime side specificity of dengue protease substrates was investigated by use of proteochemometrics, a technology for drug target interaction analysis. A set of 48 internally quenched peptides were designed using statistical molecular design (SMD) and assayed with proteases of four subtypes of dengue virus (DEN-1-4) for Michaelis (K(m)) and cleavage rate constants (k(cat)). The data were subjected to proteochemometrics modeling, concomitantly modeling all peptides on all the four dengue proteases, which yielded highly predictive models for both activities. Detailed analysis of the models then showed that considerably differing physico-chemical properties of amino acids contribute independently to the K(m) and k(cat) activities. For k(cat), only P1' and P2' prime side residues were important, while for K(m) all four prime side residues, P1'-P4', were important. The models could be used to identify amino acids for each P' substrate position that are favorable for, respectively, high substrate affinity and cleavage rate.

Keywords
dengue proteases, proteochemometrics, substrate library, peptide library, library design, statistical molecular design, molecular recognition modeling
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-104207 (URN)10.1016/j.bmc.2008.08.081 (DOI)000259973200034 ()18824362 (PubMedID)
Available from: 2009-05-27 Created: 2009-05-27 Last updated: 2018-01-13Bibliographically approved
Mandrika, I., Prusis, P., Yahorava, S., Tars, K. & Wikberg, J. E. S. (2007). QSAR of multiple mutated antibodies. Journal of Molecular Recognition, 20(2), 97-102
Open this publication in new window or tab >>QSAR of multiple mutated antibodies
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2007 (English)In: Journal of Molecular Recognition, ISSN 0952-3499, E-ISSN 1099-1352, Vol. 20, no 2, p. 97-102Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to develop predictive quantitative structure-activity relationship (QSAR) modeling for antibody-peptide interactions. A small single chain antibody library was designed and manufactured around the murine anti-p24 (HIV-1) monoclonal antibody CB4-1 by use of statistical molecular design (SMD) principles and site directed mutagenesis, and its affinity for a p24 derived antigen was determined by fluorescence polarization. A satisfactory QSAR model (Q2 = 0.74, R2 = 0.88) was derived by correlating the affinity data to physicochemical property scales of the amino acids varied in the library. The model explains most of the antibody-antigen interactions of the studied set, and provides insights into the molecular mechanism involved in antigen binding.

Keywords
Amino acid physicochemical properties, Antibody library, Interaction site mapping, Peptide epitope, QSAR, Single chain antibody, Site directed mutagenesis, Statistical molecular design
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-15889 (URN)10.1002/jmr.817 (DOI)000246169000004 ()17421049 (PubMedID)
Available from: 2008-06-05 Created: 2008-06-05 Last updated: 2018-01-12Bibliographically approved
Lapinsh, M., Veiksina, S., Uhlén, S., Petrovska, R., Mutule, I., Mutulis, F., . . . Wikberg, J. E. (2005). Proteochemometric mapping of the interaction of organic compounds with melanocortin receptor subtypes. Molecular Pharmacology, 67(1), 50-59
Open this publication in new window or tab >>Proteochemometric mapping of the interaction of organic compounds with melanocortin receptor subtypes
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2005 (English)In: Molecular Pharmacology, ISSN 0026-895X, E-ISSN 1521-0111, Vol. 67, no 1, p. 50-59Article in journal (Refereed) Published
Abstract [ar]

Proteochemometrics was applied in the analysis of the binding of organic compounds to wild-type and chimeric melanocortin receptors. Thirteen chimeric melanocortin receptors were designed based on statistical molecular design; each chimera contained parts from three of the MC(1,3-5) receptors. The binding affinities of 18 compounds were determined for these chimeric melanocortin receptors and the four wild-type melanocortin receptors. The data for 14 of these compounds were correlated to the physicochemical and structural descriptors of compounds, binary descriptors of receptor sequences, and cross-terms derived from ligand and receptor descriptors to obtain a proteochemometric model (correlation was performed using partial least-squares projections to latent structures; PLS). A well fitted mathematical model (R(2) = 0.92) with high predictive ability (Q(2) = 0.79) was obtained. In a further validation of the model, the predictive ability for ligands (Q(2)lig = 0.68) and receptors (Q(2)rec = 0.76) was estimated. The model was moreover validated by external prediction by using the data for the four additional compounds that had not at all been included in the proteochemometric model; the analysis yielded a Q(2)ext = 0.73. An interpretation of the results using PLS coefficients revealed the influence of particular properties of organic compounds on their affinity to melanocortin receptors. Three-dimensional models of melanocortin receptors were also created, and physicochemical properties of the amino acids inside the receptors' transmembrane cavity were correlated to the PLS modeling results. The importance of particular amino acids for selective binding of organic compounds was estimated and used to outline the ligand recognition site in the melanocortin receptors.

National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-104286 (URN)10.1124/mol.104.002857 (DOI)15470082 (PubMedID)
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2018-01-13Bibliographically approved
Mutulis, F., Yahorava, S., Mutule, I., Yahorau, A., Liepinsh, E., Kopantshuk, S., . . . Wikberg, J. E. (2004). New substituted piperazines as ligands for melanocortin receptors. Correlation to the X-ray structure of. J Med Chem, 47(18), 4613-26
Open this publication in new window or tab >>New substituted piperazines as ligands for melanocortin receptors. Correlation to the X-ray structure of
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2004 (English)In: J Med Chem, ISSN 0022-2623, Vol. 47, no 18, p. 4613-26Article in journal (Refereed) Published
Keywords
Animals, Cell Line, Crystallography; X-Ray, Heterocyclic Compounds with 4 or More Rings/*chemistry/pharmacology, Humans, Ligands, Magnetic Resonance Spectroscopy, Models; Molecular, Molecular Structure, Piperazines/*chemistry/pharmacology, Protein Binding, Radioligand Assay, Receptors; Melanocortin/*agonists, Research Support; Non-U.S. Gov't, Structure-Activity Relationship
Identifiers
urn:nbn:se:uu:diva-72389 (URN)15317471 (PubMedID)
Available from: 2007-01-31 Created: 2007-01-31 Last updated: 2011-01-12
Mutulis, F., Erdelyi, M., Mutule, I., Kreisberga, J., Yahorava, S., Yahorau, A., . . . Wikberg, J. (2003). 2-(p-Hydroxybenzyl)indoles - side products formed upon cleavage of indole derivatives from carboxylated Wang polymer- an NMR study.. Molecules, 8, 728-734
Open this publication in new window or tab >>2-(p-Hydroxybenzyl)indoles - side products formed upon cleavage of indole derivatives from carboxylated Wang polymer- an NMR study.
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2003 (English)In: Molecules, Vol. 8, p. 728-734Article in journal (Other scientific) Published
Identifiers
urn:nbn:se:uu:diva-72288 (URN)
Available from: 2005-05-20 Created: 2005-05-20 Last updated: 2011-01-13
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