An approach to cyclic peptide libraries: Reducing epimerization in medium sized rings during solid phase synthesis

Abstract

Using an amino acid linked by its side chain to a solid support, head-to-tail cyclic peptide libraries of varying ring size have been prepared via resin-bound cyclization. These mixtures complement the use of linear peptide libraries for drug lead discovery and extend molecular diversity to conformationally constrained systems. During our synthesis of cyclic peptide mixtures, C-terminal epimerization was identified as a problem during chain elongation. This was significantly overcome by coupling with preactivated amino acid pentafluorophenyl esters.