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

Two dipeptide isosteres 7-exo-BTG (1) and 7-endo-BtA (2), belonging to the new class of y/delta -bicyclic amino acid BTAa, were inserted into an 1 I-r esidue peptide deriving from the Bowman Birk Inhibitor (BBI) class of serin e protease inhibitors, and the conformational properties of these modified peptides have been studied by NMR and molecular modelling. The dipeptide is ostere 7-endo-BtA [(1R,4S,5R,7R)-4-endo-methyl-6,8-dioxa-3-azabicyclo[3.3.1 ]octane-7-endo-carboxylic acid] (2), derived from L-alanine and meso tartar ic acid, gave rise to the modified BBI peptide 5 whose structure was very s imilar to that of the original peptide 3, suggesting a possible reverse tur n inducing property for this dipeptide isostere. (C) 2001 Elsevier Science Ltd. All rights reserved.