Synthesis Of Cyclic Peptides And Peptide Libraries On A New Disulfide Linker

A new cysteine-based disulfide linker for Fmoc solid phase peptide synthesis was developed (Fmoc-Cys(3-mercapto-3methylbutanoic acid)OPp) that allows the on-resin assembly and side chain deprotection of cyclic peptides. Model peptides and a cyclic peptide library of the structure [a-a-x-x-a-a-c] composed of D-amino acids were assembled and the synthesis and cleavage conditions studied. The best cyclization results were obtained with PyBOP/HOAt/diisopropylethyl amine. Racemization rates of the cysteine in the analyzed model sequences were between 5.2 and 12.3%. Cleavage of the disulfide bond was best carried out with DTT in 50% 2-propanol/ 100 mm ammonium bicarbonate. The cleaved peptides can be used directly in biological assays. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.