Nazumazoles D-F，抑制糜蛋白酶的环状五肽，来自海绵 Theonella swinhoei。

Nazumazoles D-F, Cyclic Pentapeptides That Inhibit Chymotrypsin, from the Marine Sponge Theonella swinhoei.

机构信息

Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Bunkyo-ku, Tokyo 113-8657, Japan.

出版信息

J Nat Prod. 2016 Jun 24;79(6):1694-7. doi: 10.1021/acs.jnatprod.6b00261. Epub 2016 May 23.

DOI:10.1021/acs.jnatprod.6b00261

PMID:27213234

Abstract

Nazumazoles D-F (1-3) were isolated from the marine sponge Theonella swinhoei. The compounds gave extremely broad peaks by reversed-phase HPLC using an ODS column. HPLC using a gel permeation column was instrumental for the separation of the three compounds. Their planar structures were determined by interpretation of NMR data to be cyclic pentapeptides. Nazumazoles D-F contained one residue each of α-keto-l-norvaline (l-Knv) {or α-keto-d-leucine (l-Kle)}, l-alanyloxazole (l-Aox), d-Abu (or d-Ser), N-α-CHO-β-l-Dpr, and cis-4-methyl-l-proline. The absolute configuration of each amino acid residue was determined by Marfey's method in combination with conversion of the α-keto-β-amino acid to the α-amino acid by oxidation. Nazumazoles D-F are not cytotoxic against P388 cells at 50 μM, but inhibit chymotrypsin.

摘要

Nazumazoles D-F（1-3）从海绵 Theonella swinhoei 中分离得到。这些化合物在反相 HPLC 中使用 ODS 柱得到非常宽的峰。使用凝胶渗透柱的 HPLC 对于三种化合物的分离非常重要。通过对 NMR 数据的解释确定了它们的平面结构为环状五肽。Nazumazoles D-F 分别含有一个 α-酮-l-正缬氨酸（l-Knv）{或 α-酮-d-亮氨酸（l-Kle)}、l-丙氨酰恶唑（l-Aox）、d-Abu（或 d-Ser）、N-α-CHO-β-l-Dpr 和顺式-4-甲基-l-脯氨酸。每个氨基酸残基的绝对构型通过 Marfey 法结合氧化将 α-酮-β-氨基酸转化为 α-氨基酸来确定。Nazumazoles D-F 在 50 μM 时对 P388 细胞没有细胞毒性，但抑制胰凝乳蛋白酶。