含磷的血管紧张素转换酶抑制剂。
Phosphorus-containing inhibitors of angiotensin-converting enzyme.
作者信息
Thorsett E D, Harris E E, Peterson E R, Greenlee W J, Patchett A A, Ulm E H, Vassil T C
出版信息
Proc Natl Acad Sci U S A. 1982 Apr;79(7):2176-80. doi: 10.1073/pnas.79.7.2176.
Abstract
Several phosphonamides, phosphoramides, and phosphates having the general structure R-Y-P(O)(OH)-X-CH(CH3)-CO-Pro have been synthesized and tested for inhibition of angiotensin-converting enzyme (dipeptidyl carboxypeptidase; peptidyl-dipeptide hydrolase, EC 3.4.15.1). Inhibition was found to depend on the nature of R, Y, and X such that the maximal effect was observed when X = NH, Y = CH2, and R = phi CH2 (50% inhibition at 7 nM). Substitution of CH2 or O at X and O at Y produced significantly less potent inhibitors. Groups shorter or longer than R = phi CH2 led to less active inhibitors, presumably due to nonoptimal interaction of the side chain with the S1 subsite.
摘要
已经合成了几种具有通式R-Y-P(O)(OH)-X-CH(CH3)-CO-Pro的磷酰胺、磷酰酰胺和磷酸盐，并测试了它们对血管紧张素转换酶（二肽基羧肽酶；肽基二肽水解酶，EC 3.4.15.1）的抑制作用。发现抑制作用取决于R、Y和X的性质，当X = NH、Y = CH2且R = phi CH2时观察到最大效果（在7 nM时50%抑制）。在X处用CH2或O取代以及在Y处用O取代会产生效力明显较低的抑制剂。比R = phi CH2短或长的基团导致活性较低的抑制剂，推测是由于侧链与S1亚位点的相互作用不理想。
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1
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Prog Med Chem. 1980;17:41-104. doi: 10.1016/s0079-6468(08)70157-7.
2
Inhibition of angiotensin converting enzyme with N alpha-phosphoryl-L-alanyl-L-proline and N alpha-L-valyl-L-tryptophan.用Nα-磷酰-L-丙氨酰-L-脯氨酸和Nα-L-缬氨酰-L-色氨酸抑制血管紧张素转换酶
Biochem Biophys Res Commun. 1980 Nov 17;97(1):94-9. doi: 10.1016/s0006-291x(80)80139-2.
3
Synthesis and biological activity of a ketomethylene analogue of a tripeptide inhibitor of angiotensin converting enzyme.血管紧张素转换酶三肽抑制剂的酮亚甲基类似物的合成与生物活性
J Med Chem. 1980 Dec;23(12):1392-8. doi: 10.1021/jm00186a020.
4
Esterase activity of rabbit pulmonary angiotensin converting enzyme.
Biochem Biophys Res Commun. 1980 Sep 16;96(1):506-13. doi: 10.1016/0006-291x(80)91243-7.
5
A new class of angiotensin-converting enzyme inhibitors.一类新型的血管紧张素转换酶抑制剂。
Nature. 1980 Nov 20;288(5788):280-3. doi: 10.1038/288280a0.
6
[Synthesis of desoxyoligonucleotides with trichlorethyl-phosphate-protecting groups].[用三氯乙基磷酸酯保护基团合成脱氧寡核苷酸]
Chem Ber. 1968;101(3):944-53. doi: 10.1002/cber.19681010326.
7
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J Antibiot (Tokyo). 1973 Oct;26(10):621-3. doi: 10.7164/antibiotics.26.621.
8
An angiotensin converting-enzyme inhibitor to identify and treat vasoconstrictor and volume factors in hypertensive patients.一种用于识别和治疗高血压患者血管收缩和容量因素的血管紧张素转换酶抑制剂。
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Arch Biochem Biophys. 1975 Dec;171(2):727-31. doi: 10.1016/0003-9861(75)90085-5.
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