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Search for serine protease inhibitors from marine invertebrates.

从海洋无脊椎动物中寻找丝氨酸蛋白酶抑制剂。

基本信息

批准号：
03454088
负责人：
FUSETANI Nobuhiro
金额：
$ 4.16万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454088/
关键词：
Marine Invertebrates Protease Inhibitors Thrombin Trypsin Serine Proteases Marine Sponges Nazumamide A Toxadocial A 海綿動物 toxadocial A 硫酸コステルセリンプロテア-ゼ nazumomide A テトラペプチド

项目摘要

Marine sponges (273 samples), coelenterates (32 samples), bryozoans (7 samples) and tunicates (26 samples) were collected from the Izu Peninsula, Hachijo Island, Kyushu and Shikoku. The hot methanol extracts of samples were partitioned between H_2O and CHCl_3 to give organic and aqueous layers. Each layer was assayed for inhibitory activities against thrombin and trypsin. Forty-five samples of sponges, 5 of coelenterates and 5 of tunicates were active. Genrally, activities were found in the aqueous layers, but some organic layers showed activities.One of active sponge sample, Theonella swinhoei was extracted, and the extract was fractionated to obtain a thrombin inhibitor named nazumamide A, which inhibited thrombin at an IC_<50> of 2.8 mug/mL. Amino acids analysis and spectral analyses including 2D NMR and FABMS led to a tetrapeptide possessing the N-2,5-dihydroxybenzoate terminus (1).Another active sponge Toxadocia cylindrica was similarly processed to yield a thrombin inhibitor, toxadocial A, which inhibited thrombin at an IC_<50> of 6.5 mug/mL. The structure elucidation was carried out by means of spectral analyses and chemical transformation to obtain an unusual tetrasulfated aldehyde as shown (2)

从伊豆半岛、八丈岛、九州和四国采集海绵（273个样品）、腔肠动物（32个样品）、苔藓虫（7个样品）和被囊动物（26个样品）。样品的热甲醇提取物在H_2O和CHCl_3之间分配，得到有机层和水层。测定各层对凝血酶和胰蛋白酶的抑制活性。45个海绵样本、5个腔肠动物样本和5个被囊动物样本具有活性。从活性海绵样品Theonella swinhoei中提取一种凝血酶抑制剂，经分级分离得到一种凝血酶抑制剂nazumamide A，其抑制凝血酶的IC_2<50>为2.8 μ g/mL。氨基酸分析和光谱分析（包括2D NMR和FABMS）导致具有N-2，5-二羟基苯甲酸酯末端的四肽（1）。另一种活性海绵Toxadocia cylindrica被类似地处理以产生凝血酶抑制剂toxadocial A，其抑制凝血酶的IC_<50>为6.5 μ g/mL。通过光谱分析和化学转化进行了结构鉴定，得到了一种不寻常的四硫酸化醛，如（2）所示。