Cristina Tiozzo, Federico Squassabia, Alessandra Tolomelli, Luca Gentilucci and Giuliana Cardillo Pages 395 - 400 ( 6 )
The surface loops of proteins and active peptides are implicated in the activation of biological responses upon recognition by enzymes and receptors. Obviously, it is of interest to investigate these loops as potential leads for drug discovery. Currently, there is an urgent need for novel, general, and conformationally definite cyclic peptidomimetic scaffolds capable to mimic small portions of the protein surface. In this respect, 13-membered ring peptidomimetics can be considered privileged structures, since they represent the smallest possible systems that can retain all of the features of organized protein structures, such as single H-bonded alfa-helix loops and different kind of turns. In the present work, we report a novel family of 13-membered ring cyclic peptidomimetics based on a minimal PMRI (partially modified retro-inverse) peptide strategy; in particular, we describe the synthesis and the conformational analysis of a representative member of the family. These scaffolds have been designed to permit easy introduction in a combinatorial fashion of a range of pharmacophores that possess a diversity of structure, function, and 3D disposition.
cyclic peptide, PMRI peptide, peptidomimetic, scaffold, molecular diversity
Department of Chemistry G.Ciamician, Universita degli Studi di Bologna, via Selmi 2, 40126-Bologna, Italy.