Inactivation of gamma-aminobutyric acid aminotransferase by (S,E)-4-amino-5-fluoropent-2-enoic acid and effect on the enzyme of (E)-3-(1-aminocyclopropyl)-2-propenoic acid.
Inactivation of gamma-aminobutyric acid aminotransferase by (S,E)-4-amino-5-fluoropent-2-enoic acid and effect on the enzyme of (E)-3-(1-aminocyclopropyl)-2-propenoic acid.
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(S,E)-4-氨基-5-氟戊-2-烯酸灭活 γ-氨基丁酸转氨酶以及对 (E)-3-(1-氨基环丙基)-2-丙烯酸酶的影响。
DOI：
10.1021/jm00160a007
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发表时间：
1986
影响因子：
7.3
通讯作者：
Mathew,J
中科院分区：
文献类型：
--
作者：
Silverman,RB;Invergo,BJ;Mathew,J
有时，在酶灭活剂和底物的骨架中引入双键会增加它们与靶酶的结合。（E）-2，4-二氨基-2-（氟甲基）辛-3-烯酸显示为比饱和化合物2-（氟甲基）鸟氨酸更有效的鸟氨酸脱羧酶灭活剂; 15（E）-1，4-二氨基丁-2-烯与鸟氨酸脱羧酶的结合比其饱和类似物腐胺好104倍。16由于（E）-4-氨基丁-2-烯酸作为-Abu-T的底物的活性几乎是-Abu的两倍，17合成（S，E）-4-氨基-5-氟戊-2-烯酸（方案I，6）并研究其对-Abu-T的失活。这些结果报告在这里。此外，还合成了6灭活-Abu-T可能中间体的环丙基类似物。本文还报道了（E）-3-（1-氨基环丙基）-2-丙烯酸（方案II，13）的合成和对-Abu-T的影响。（S，2？）-的合成4-氨基-5-氟戊-2-烯酸（6）。以（S）-4-氨基-5-氟戊酸（1）为原料，经六步反应合成了（S，E）-4-氨基-5-氟戊-2-烯酸。合成路线概述于方案I中。基于5（15 Hz）和6（16 Hz）的NMR谱中的烯属反式偶合常数，确定双键的立体化学为E。假设1中的C-4的手性保持完整，因为合成中的任何步骤都没有
Sometimes the incorporation of a double bond into the backbone of enzyme inactivators and substrates increases their binding to thetarget enzyme.(£)-2, 4-Diamino-2-(fluoromethyl) pent-3-enoic acid was shown to be a more potent inactivator of ornithine decarboxylase than the saturated compound, 2-(fluoromethyl) ornithine; 15 (E)-l, 4-diaminobut-2-ene binds 104 times better to ornithine decarboxylase than does its saturated analogue, putres-cine. 16 Since (£)-4-aminobut-2-enoic acid is almost twice as active a substrate for-Abu-T as is-Abu, 17 (S,£)-4-amino-5-fluoropent-2-enoic acid (Scheme I, 6) was syn-thesized and its inactivation of-Abu-T investigated. These results are reported here. Furthermore, the cyclo-propyl analogue of a possible intermediate in theinactivation of-Abu-T by 6 was synthesized. The synthesis and effect of (£)-3-(l-aminocyclopropyl)-2-propenoic acid (Scheme II, 13) on-Abu-T also are reported here. Results and DiscussionSynthesis of (S, 2?)-4-Amino-5-fluoropent-2-enoic Acid (6). The synthesis of (S,£)-4-amino-5-fluoropent-2-enoic acid was carried out in sixsteps from (S)-4-amino-5-fluoropentanoic acid (l). 10 The synthetic route is outlined in Scheme I. The stereochemistry of the double bond was determined to be E on the basis of the olefinic trans coupling constants in the NMR spectra of 5 (15 Hz) and 6 (16 Hz). It is assumed that the chirality of C-4 in 1 remains intact because none of the steps in the synthesis