Straightforward strategy to substitute amide bonds by 1,2,3-triazoles in peptaibols analogs using Aibψ[Tz]-Xaa dipeptides

Biopolymers, 2015, Volume: 104, Issue: 5, Pages: 611-621, DOI: 10.1002/bip.22641

K. Ben Haj Salah, B. Legrand, S. Das, J. Martinez, N. Inguimbert


Structured peptides have gained more attention over time because of their biol. properties, biocompatibility and ability to act as modulators of protein/protein interactions, antibiotics, analgesics, immunosuppressants, and imaging agents to cite a few relevant applications.  However, their poor bioavalability due in part to the susceptibility of the peptide bond to proteolytic cleavages has often impaired their development and considerably limited their therapeutic use.  To circumvent these problems, many efforts have been undertaken to discover stable amide bond mimics resistant to proteolytic degrdn.  Among them the 1,2,3-triazole (Tz) moiety has emerged as a highly stable analog of the trans-peptide bond as a means of generating bioactive peptides.  Here we report a convenient approach to readily substitute amide bonds by triazole rings in Aib-contg. peptides using Aibψ[Tz]-Xaa dipeptide-like units.  We have defined their application in solid phase synthesis and generated short model peptide sequences to study the impact of triazole incorporation on their conformations in soln. by CD and NMR spectroscopies.  © 2015 Wiley Periodicals, Inc.  Biopolymers (Pept Sci) 104: 611-621, 2015.