Analogues of cyclolinopeptide a containing α-hydroxymethyl amino acid residues

✍ Scribed by Paweł Zubrzak; Agnieszka Banaś; Krzysztof Kaczmarek; Mirosław T. Leplawy; Marek Sochacki; Marek L. Kowalski; Barbara Szkudlińska; Janusz Zabrocki; Paola Di Lello; Carla Isernia; Michele Saviano; Carlo Pedone; Ettore Benedetti

• Publisher: Wiley (John Wiley & Sons)
• Year: 2005
• Tongue: English
• Weight: 190 KB
• Volume: 80
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.20182

✦ Synopsis

Abstract

Linear and cyclic cyclolinopeptide A (CLA) analogues containing α‐hydroxymethylleucine (HmL) in positions 1, 4, and 1&4, and α‐hydroxymethylvaline (HmV) in position 5, were synthesized by the solid‐phase peptide strategy and cyclized with the 1‐Ethyl‐3‐(3‐dimethylaminopropyl)‐carbodiimide/1‐hydroxy‐7‐azabenzotriazole (EDC/HOAt) reagent. The peptides were examined for their immunosuppressive activity in the lymphocyte proliferation assays (LPA). Only HmL‐containing peptides demonstrated at about 25% lower immunosuppressive activity, but they are four times more soluble in water solutions than the native CLA. It seems from the LPA results that peptide [(HmL^4^)CLA] is the most promising for further studies. This peptide was characterized in solution, at room temperature in CDCl~3~, and the conformation compared with that observed for CLA in the solid state. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005