Synthesis of cyclic peptides and peptide libraries on a new disulfide linker

✍ Scribed by Werner Tegge; Wilfried Bautsch; Ronald Frank

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 261 KB
• Volume: 13
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.879

✦ Synopsis

Abstract

A new cysteine‐based disulfide linker for Fmoc solid phase peptide synthesis was developed (Fmoc‐Cys(3‐mercapto‐3‐methylbutanoic 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 © 2007 European Peptide Society and John Wiley & Sons, Ltd.