著者

横尾 信夫 服部 英三 平田 光輝 渡辺 好一郎 佐藤 文泰 永倉 正彦 藤井 節郎

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.107, no.9, pp.732-737, 1987-09-25 (Released:2008-05-30)

参考文献数

9

被引用文献数

1 1

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Synthesis of water-soluble chymotrypsin specific inhibitors was attempted to study the roles of chymotrypsin-like enzymes in vivo. Previously we reported that the esters of carboxylic acid containing a condensed ring showed stronger activity than those containing a single ring system. Then we synthesized 4-substituted phenyl esters of carboxylic acid containing a condensed ring, such as tetralin, naphthalene, indole etc., and their inhibitory activities were compared. Among these compounds, esters of tetralin-1-carboxylic acid (FK-448) and 1-naphthylacetic acid showed the strongest activity, and their IC50 values were 8×10-7, 5×10-7 M, respectively. Tetralin-2-carboxylate and 2-naphthylacetate inhibited weaker than 1-analogues. Esters of basic quinoline carboxylic acid and bulky carboxylic acids containing a three-ring system inhibited poorly. Chymotrypsin produced equimolecular 4-substituted phenol rapidly and thereafter the amount of 4-substituded phenol increased slowly, when incubated with FK-448 at 37°C.

著者

枝野 敏行 新井 晃一 大島 武 古志 朋之 平田 光輝 大口 正夫 岡部 哲郎

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.17, no.3, pp.379-382, 1994-03-15

被引用文献数

4

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In order to identify the membrane-bound peptidase that is responsible for the degradation of endothelin (ET), an endothelin-1 (ET-1) degradation enzyme was solubilized from membrane fractions of porcine kidney with 1% Triton X-100,and subsequently purified by column chromatographies, i. e., diethylamino-Sepharose ion exchange, gel permeation, Con A Sepharose and hydroxyapatite chromatography. On DEAE-Toyopearl ion exchange column chromatography, the ET degradation enzyme and aminopeptidase were separated, but ET degradation enkephalinase activities were not separable. In order to separate ET degradation enzyme and enkephalinase, the active fractions were loaded on each of the column chromatographies : sephacryl S-200,Con A Sepharose or hydroxyapatite. The ET degradation activities were co-migrated with enkephalinase activities on all of the three chromatographies. In addition, the ET degradation activities were inhibited by thiorphan, phosphoramidon and EDTA, which are known to inhibit enkephalinase. These results suggest that ET degradation activity in the membrane fractions of the kidney is related to enkephalinase and may be involved in the degradation of ET-1 in vivo.