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

Dariusz Sobolewski, Adam Prahl, Anna Kwiatkowska, Jirina Slaninová, Bernard Lammek

Index: J. Pept. Sci. 15 , 161-165, (2009)

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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 alpha-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 invitro activities in the rat.