title: Structure-activity relationship of marinostatin, a serine protease inhibitor isolated from a marine organism.
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 beta-hydroxyl and beta-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.
authors.affiliation: SAITO Research Center, Peptide Institute, Inc., Ibaraki, Osaka 567-0085, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Taichi
authors.forename: Tohimasa
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kawahara
authors.forename: Daisuke
authors.initials: D
authors.lastname: Motooka
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.forename: Shusaku
authors.initials: S
authors.lastname: Harada
authors.forename: Tadashi
authors.initials: T
authors.lastname: Teshima
authors.forename: Tadayasu
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishiuchi
mesh_terms: D000818:Animals; D015195:Drug Design; D008386:Marine Biology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D010456:Peptides, Cyclic; D015842:Serine Proteinase Inhibitors; C073224:marinostatin D