Analogues of AVP modified in the N-terminal part of the molecule with Pip isomers: TFA-catalysed peptide bond hydrolysis

✍ Scribed by Dariusz Sobolewski; Adam Prahl; Anna Kwiatkowska; Jiřina Slaninová; Bernard Lammek

• Book ID: 105359729
• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 121 KB
• Volume: 15
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.1094

✦ Synopsis

Abstract

Using SPPS techniques, six new analogues of AVP and some of its agonists were synthesised. The peptides were designed by substitution of Phe at position 3 of AVP, [Mpa^1^] AVP (dAVP) and [Mpa^1^,Val^4^,D‐Arg^8^]VP (dVDAVP) with L‐ or D‐Pip, a non‐coded α‐imino acid, also called homoproline. Surprisingly enough, both the analogues of AVP and [Mpa^1^]AVP with identical substituents at position 2 turned out to be highly sensitive to TFA used for deprotection and cleavage of the synthesised peptides from the resin and it was the reason why we were not able to obtain these four peptides. The mechanisms of their fragmentation were proposed in this study. Unfortunately, all the new analogues were inactive in bioassays for the pressor, antidiuretic and uterotonic in____vitro activities in the rat. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.