AN APPROACH TO CYCLIC PEPTIDE LIBRARIES - REDUCING EPIMERIZATION IN MEDIUM-SIZED RINGS DURING SOLID-PHASE SYNTHESIS

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 prepar ed via resin-bound cyclization. These mixtures complement the use of l inear peptide libraries for drug lead discovery and extend molecular d iversity to conformationally considered 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.