We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
α-Aminoxy acids as building blocks for the oxime and hydroxylamine pseudopeptide links. Application to the synthesis of human elastase inhibitors.
- Authors
Regis Vanderesse; Laurent Thevenet; Michel Marraud; Nicole Boggetto; Michele Reboud; Catherine Corbier
- Abstract
The aminoxy acids NH2OCαHRCO2H are much more easily obtained in the enantiomerically pure form than the analogous hydrazino acids NH2NHCαHRCO2H, and it has been shown that the isosteric amidoxy ψ[CONHO] and hydrazide ψ[CONHNH] amide surrogates induce two quite similar γ-like folded structures. An aminoxy acid can also be N-coupled to a peptide aldehyde to give the aldoxime ψ[CH=NOO] link or to a peptide ketone to form the ketoxime ψ[CR=N O] link. The former can be further reduced into the hydroxylamine ψ[CH2NHO] link which gives rise to reduced amidoxy peptides. The structural properties induced by these amide surrogates were studied, using IR and NMR spectroscopy, paying particular attention to the Z/E-isomerism of the oxime link. In order to investigate their inhibitory potency, the three amide surrogates were introduced in the Pro3-Val4 and Val4-Ala5 position of Z-Ala1-Ala2-Pro3-Val4-Ala5-Ala6-NHiPr, a substrate which is cleaved in the Val4-Ala5 position by human leukocyte elastase (HLE). The [Val4ψ[CONHO]Ala5] analogue was still a substrate, while the [Pro3ψ[CONHO]Val4] and [Val4ψ[CH=NO]Ala5] pseudopeptides acted as HLE competitive inhibitors. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
- Subjects
PEPTIDES; PROTEINS; ALDEHYDES; HYDROXYLAMINE; KETONES; KETONIC acids
- Publication
Journal of Peptide Science, 2003, Vol 9, Issue 5, p282
- ISSN
1075-2617
- Publication type
Article
- DOI
10.1002/psc.452