Structure–activity relationship of marinostatin, a serine protease inhibitor isolated from a marine organism

✍ Scribed by Misako Taichi; Tohimasa Yamazaki; Kazuki Kawahara; Daisuke Motooka; Shota Nakamura; Shusaku Harada; Tadashi Teshima; Tadayasu Ohkubo; Yuji Kobayashi; Yuji Nishiuchi

• Book ID: 105359874
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 280 KB
• Volume: 16
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.1244

✦ Synopsis

Abstract

A 12‐residue MST isolated from a marine organism is a potent serine protease inhibitor that has a double cyclic structure composed of two ester linkages formed between the β‐hydroxyl and β‐carboxyl groups, Thr^3^‐Asp^9^ and Ser^8^‐Asp^11^. MST was synthesized by a regioselective esterification procedure employing two sets of orthogonally removable side‐chain protecting groups for the Asp and Ser/Thr residues. In the MST molecule, there were no significant changes observed in yield by changing the order of esterification. SAR study of MST revealed that the minimum required structure for expressing the inhibitory activity is the sequence (1–9) in a monocyclic structure where Pro^7^ located in the ring plays a crucial role in keeping the structural rigidity. By applying the structural motif of MST, we rationally designed protease inhibitory specificities that differ from those of the natural product. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.