Inhibition of chymotrypsin by fluorinated alpha-keto acid derivatives.
Inhibition of chymotrypsin by fluorinated alpha-keto acid derivatives.
复制标题
氟化α-酮酸衍生物抑制胰凝乳蛋白酶。
DOI：
10.1021/bi00154a015
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发表时间：
1992
期刊：
影响因子：
2.9
通讯作者：
Abeles,RH
中科院分区：
文献类型：
--
作者：
Parisi,MF;Abeles,RH
n-糜蛋白酶（II型，来自牛胰腺）、弹性蛋白酶（I型，来自牛胰腺）、木瓜蛋白酶（来自木瓜胶乳）、胰蛋白酶（XI型，来自牛胰腺）、1-，1 MeO-Suc-AAPV-pNA、Suc-AAPF-pNA和Cbz-Ala-Leu-OH购自Sigma Chemical Co.。该程序由Ayi et al.（1981），用于合成3-氟-3-苯基-丙酮酸甲酯和3-氟-3-苄基丙酮酸甲酯（4a，B）和相应的酸5a，B的方法概述于方案I中。根据这一策略，苯甲醛（1a）和苯乙醛（1b）与氯乙酸甲酯通过Darzen缩水甘油酸酯缩合得到环氧酯2a，B。2a，B用氟化氢-吡啶溶液开环生成β-氟-α-羟基酯3a，B，它们被氧化成4a，B，然后水解成β-酮酸5a，B。缩写：I-BAPNA，TVa-苯甲酰基-L-精氨酸对硝基苯胺盐酸盐; MeOSuc-AAPV-pNA，N-甲氧基琥珀酰基-L-丙氨酰基-L-丙氨酰基-L-脯氨酰基-L-缬氨酸对硝基苯胺; Suc-AAPF-pNA，TV-琥珀酰基-L-丙氨酰基-L-丙氨酰基-L-脯氨酰基-L-苯丙氨酸对硝基苯胺; Tris，tris（羟甲基）氨基甲烷; 4-APPA，（4-脒基苯基）烟酸; Ac，乙酰基; Bz，苯甲酰基; Cbz，苄氧羰基; DCC，1，3-二环己基碳二亚胺; DME，二甲氧基乙烷。
MATERIALS AND METHODS«-Chymotrypsin (type II, from bovine pancreas), elastase (type I, from bovine pancreas), papain (from papaya latex), trypsin (type XI, from bovine pancreas), l-, 1 MeO-Suc-AAPV-pNA, Suc-AAPF-pNA, and Cbz-Ala-Leu-OH were purchased from Sigma Chemical Co. Methyl benzoylformate and sodium phenylpyruvate monohydrate were obtained fromAldrich Chemical Co. Inhibitor Synthesis. The procedure, developed by Ayi et al.(1981), for the synthesis of methyl 3-fluoro-3-phenyl-and methyl 3-fluoro-3-benzylpyruvate (4a, b) and the correspond-ing acids 5a, b is outlined in Scheme I. Accordingto this strategy, epoxyesters 2a, b were obtained by Darzen glycidic ester condensation of benzaldehyde (la) and phenylacetal-dehyde (lb) with methylchloroacetate. Ring opening of 2a, b with a hydrogen fluoride-pyridine solutionproduced the/3-fluoro-a-hydroxy esters 3a, b, which were oxidized to 4a, b and then hydrolyzed to the-keto acids 5a, b. Methyl phenylpyruvate (9b) was obtained by methylation of the1 Abbreviations: l-BAPNA, TVa-benzoyl-L-arginine p-nitroanilide hydrochloride; MeOSuc-AAPV-pNA, N-methoxysuccinyl-L-alanyl-L-alanyl-L-prolyl-L-valine p-nitroanilide; Suc-AAPF-pNA, TV-succinyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanine p-nitroanilide; Tris, tris (hy-droxymethyl) aminomethane; 4-APPA,(4-amidinophenyl) pyruvic acid; Ac, acetyl; Bz, benzoyl; Cbz, carbobenzyloxy; DCC, 1, 3-dicyclohexylcarbodiimide; DME, dimethoxyethane.