9 海綿Theonella sp.のトロンビン阻害物質cyclotheonamide AおよびB(口頭発表の部)

概要

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In the course of our screening program of Japanese marine invertebrates for potential biomedicals, a marine sponge of the genus Theonella inhibited various proteinases, particularly thrombin. We have isolated two active substances, named cyclotheonamides A and B, which proved to be novel cyclic peptides. Cyclotheonamide A was isolated from the 1987 collection by means of solvent partitioning, gel filtration, and three successive reverse-phase HPLC's, whereas cyclotheonamide B was isolated from the 1989 collection. ^1H and ^<13>C NMR spectra indicated that cyclotheonamide A contained Pro, Phe, 2,3-diaminopropionic acid (Dpr), and two unusual amino acid residues, 3 and 4. Amino acid 3 was an analog of Arg with a ketone group between the carboxyl and methane carbons. Amino acid 4 was a Tyr analog with an ethelene unit between the carboxyl and methine carbons. α-Amino group of Dpr was formylated. The sequence of the five residues was deduced by a combination of HMBC and NOESY experiments. Thus, cyclotheonamide A was cyclo[Phe-4-isoD(CHO)pr-Pro-3]. Cyclotheonamide B has an acetamide instead of formylamide in cyclotheonamide A. The stereochemistry of the amino acids except 3 was deduced by chiral GC analysis after degradation. Cyclotheonamide A inhibited thrombin with IC_<50> 0.076 ug/mL.
1990-09-25