Introduction of the new dipeptide isostere 7-endo-BtA as reverse turn inducer in a Bowman-Birk proteinase inhibitor : synthesis and conformational analysis

Abstract

Two dipeptide isosteres 7- exo-BTG ( 1) and 7- endo-BtA ( 2), belonging to the new class of γ/δ-bicyclic amino acid BTAa, were inserted into an 11-residue peptide deriving from the Bowman Birk Inhibitor (BBI) class of serine protease inhibitors, and the conformational properties of these modified peptides have been studied by NMR and molecular modelling. The dipeptide isostere 7- endo-BtA [(1 R,4 S,5 R,7 R)-4- endo-methyl-6,8-dioxa-3-azabicyclo[3.2.1]octane-7- endo-carboxylic acid] ( 2), derived from l-alanine and meso tartaric acid, gave rise to the modified BBI peptide 5 whose structure was very similar to that of the original peptide 3, suggesting a possible reverse turn inducing property for this dipeptide isostere.