Potential inhibitors of L-asparagine biosynthesis. 2. Chemistry and biological activity of beta-hydroxyaspartic acid and its derivatives.
Potential inhibitors of L-asparagine biosynthesis. 2. Chemistry and biological activity of beta-hydroxyaspartic acid and its derivatives.
复制标题
L-天冬酰胺生物合成的潜在抑制剂。
DOI：
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发表时间：
1975
影响因子：
7.3
通讯作者：
B. Parikh
中科院分区：
文献类型：
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作者：
M. Mokotoff;J. F. Bagaglio;B. Parikh
合成了几种赤霉素β-羟基-DL-天冬氨酸(1)衍生物，作为大鼠Novikoff肝癌L-天冬酰胺合成酶(ASase)的潜在抑制剂。1的苄基化得到二苄酯2，与羧基苯甲氧基甘氨酸偶联得到封闭的二肽3。解封3得到不能重氮化的甘氨酸二乙基-β-羟基天冬氨酸(4)。将1的二甲酯与羧基苯甲氧基甘氨酸偶联，得到封闭的二肽7a，解封后得到二甲基甘氨酸二乙酯-赤霉素-β-羟基-DL-天冬氨酸盐酸盐(8)。8经重氮化得到不纯重氮化合物9，再与盐酸反应得到氯化合物10。本文叙述了天冬氨酸氨基转移酶的分离、测定及抑制方法。在10 mM浓度下，10、1及其D和L对酶的抑制率分别为45%、47%、36%和66%。
Several derivatives of erythro-beta-hydroxy-DL-aspartic acid (1) were prepared as a potential inhibitors of L-asparagine synthetase (ASase) from rat Novikoff hepatoma. Benzylation of 1 gave the dibenzyl ester 2 which upon coupling with carbobenzoxyglycine afforded the blocked dipeptide 3. Deblocking of 3 gave glycl-erythro-beta-hydroxyl-DL-aspartic acid (4) which could not be diazotized. The dimethyl ester of 1 was coupled with carbobenzoxyglycine to give the blocked dipeptide 7a which was deblocked to give dimethyl glycel-erythro-beta-hydroxy-DL-aspartate hydrochloride (8). Diazotization of 8 gave impure diazo compound 9 which on reaction with HCl gave the chloro compound 10. The methods of isolation, assay, and inhibition of ASase are discribed. At 10 mM concentrations 10, 1, and its D and L enantiomers inhibit ASase by 45, 47, 36 and 66 percent, respectively.