Controlled peptide solvation in portion-mixing libraries of FRET peptides: Improved specificity determination for dengue 2 virus NS2B-NS3 protease and human cathepsin S

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dc.contributor.author Alves, Fabiana M.
dc.contributor.author Hirata, Izaura Y.
dc.contributor.author Gouvea, Iuri E.
dc.contributor.author Alves, Marcio F. M.
dc.contributor.author Meldal, Morten
dc.contributor.author Bromme, Dieter
dc.contributor.author Juliano, Luiz
dc.contributor.author Juliano, Maria A.
dc.date.accessioned 2016-01-24T13:48:51Z
dc.date.available 2016-01-24T13:48:51Z
dc.date.issued 2007-07-01
dc.identifier http://dx.doi.org/10.1021/cc070042k
dc.identifier.citation Journal of Combinatorial Chemistry. Washington: Amer Chemical Soc, v. 9, n. 4, p. 627-634, 2007.
dc.identifier.issn 1520-4766
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/29864
dc.description.abstract The solubility of peptides in aqueous buffers used for the enzyme assays is a common limitation for all peptide libraries. in principle, the more water-soluble peptides are, the more susceptible they will be to peptidase hydrolysis. We have demonstrated that this bias can be circumvented in a portion-mixing fluorescence resonance energy transfer (FRET) peptide library by introducing k (lysine in the D-form) in both termini of the peptides. This more solvated library and another one without the k were assayed using trypsin and chymotrypsin as standard peptidases with high selectivity for R and K and for hydrophobic F and Y, respectively. Significantly improved consistency of the information on substrate profiles was obtained from the solvated library. the influence of improved solvation on substrate specificity determination was successfully demonstrated by the difference in specificity observed between the two libraries employing the human cathepsin S (accepts acidic, basic, or neutral amino acids at P(1) position) and Dengue 2 virus NS2B-NS3 protease (high specificity to the pair of basic amino acids K-R, R-R, or Q-R/K at P(2)-P(1) positions). in conclusion, hydration of the peptides has a major influence on protease processing, and this bias can be reduced in bound peptide libraries, improving reliability. en
dc.format.extent 627-634
dc.language.iso eng
dc.publisher Amer Chemical Soc
dc.relation.ispartof Journal of Combinatorial Chemistry
dc.rights Acesso restrito
dc.title Controlled peptide solvation in portion-mixing libraries of FRET peptides: Improved specificity determination for dengue 2 virus NS2B-NS3 protease and human cathepsin S en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Ctr Gamle Carlsberg
dc.contributor.institution Univ British Columbia
dc.description.affiliation Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.affiliation Ctr Gamle Carlsberg, SPOCC, Carlsberg Lab, DK-2500 Copenhagen, Denmark
dc.description.affiliation Univ British Columbia, Dept Dent, Vancouver, BC V6T 1Z3, Canada
dc.description.affiliation Univ British Columbia, UBC Ctr Blood Res, Vancouver, BC V6T 1Z3, Canada
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.identifier.doi 10.1021/cc070042k
dc.description.source Web of Science
dc.identifier.wos WOS:000247820100011



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