91(P-16) アクチンを標的とする海産マクロライド類とデプシペプチド類の構造と活性(ポスター発表の部)

概要

論文の詳細を見る
The mode of action of trisoxazole macrolides, i.e. kabiramide C (1), has been characterized by fluorescent study on prodan-labeled actin. Compound 1 and related macrolides bind to G-actin in two steps, and the resulting complex is stable and long-lived. The complex also functions as a novel +end capper of F-actin and the macrolide itself acts as biomimetics of gelsolin. The absolute stereochemistry of three trisoxazole macrolides, kabiramide C (1), halichondramide (2), and ulapualide A (3), were determined by X-ray analysis on their complexes with actin. The macrolide ring binds to hydrophobic residues on subdomain 1 and the side chain portion is buried in the cleft between subdomains 1 and 3. During the isolation work, we found four new kabramide analogues (4-7) from a Thai sponge Ircinia sp. Swinholide A (8) has been found to bind to G-actin in a similar manner as trisoxazole macrolides, and to form a complex sequestering two molecules of actin as shown by X-ray crystallography. Six new depsipeptides named seragamide A-F (9-14) and a known geodiamolide I (19) have been isolated from the Okinawan sponge Suberites japonicus. The structures were elucidated with spectroscopic methods and chemical transformation. Seragamide A (9) inhibited depolymerization of F-actin and facilitated polymerization of G-actin.
天然有機化合物討論会の論文
2004-10-01