几种氨基酸膦酸酯及相关化合物对大鼠脑氨肽酶的影响。

Effect of several amino acid phosphonates and related compounds on rat brain aminopeptidases.

作者信息

Weiss B, Hui K S, Hui M, Lajtha A

机构信息

Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, New York, NY 10035.

出版信息

Res Commun Chem Pathol Pharmacol. 1987 Sep;57(3):351-8.

PMID:3671885

Abstract

N-Terminal sodium phosphonate derivatives Na3O3PCH2CONHR (R-Leu, Phe, or Tyr) and Na3O3PCH2CONHR-R (R-R = Leu-Phe, Phe-Leu, Phe-Phe, and Phe-Tyr) were synthesized. All showed no activity toward a soluble rat brain aminopeptidase. We could not prepare the corresponding N-2-phosphono-2,2-diphenylacetyl compounds (Na3O3PC(C6H5)2CONHR) by the same Arbusov reaction. Little or no inhibition was obtained with the N-(2-hydroxy-2,2-diphenylacetyl derivatives HOC(C6H5)2CONHR (R = Leu, Phe, Trp, or Tyr). The best inhibitory responses were given by the N-(2-halogeno-2,2-diphenylacetyl mono- and dipeptides (Br/Cl)C(C6H5)2CONH Phe and (Br/Cl)C(C6H5)2CONHR-R (R-R = Leu,Leu, Leu-Phe, Phe-Gly, Phe-Leu, or Phe-Phe), respectively.

摘要

合成了N-末端膦酸钠衍生物Na3O3PCH2CONHR（R =亮氨酸、苯丙氨酸或酪氨酸）和Na3O3PCH2CONHR-R（R-R =亮氨酸-苯丙氨酸、苯丙氨酸-亮氨酸、苯丙氨酸-苯丙氨酸和苯丙氨酸-酪氨酸）。所有这些化合物对可溶性大鼠脑氨肽酶均无活性。我们无法通过相同的阿尔布佐夫反应制备相应的N-2-膦酰基-2,2-二苯基乙酰化合物（Na3O3PC(C6H5)2CONHR）。N-(2-羟基-2,2-二苯基乙酰)衍生物HOC(C6H5)2CONHR（R =亮氨酸、苯丙氨酸、色氨酸或酪氨酸）几乎没有或没有抑制作用。N-(2-卤代-2,2-二苯基乙酰)单肽和二肽（Br/Cl)C(C6H5)2CONH苯丙氨酸和(Br/Cl)C(C6H5)2CONHR-R（R-R =亮氨酸、亮氨酸、亮氨酸-苯丙氨酸、苯丙氨酸-甘氨酸、苯丙氨酸-亮氨酸或苯丙氨酸-苯丙氨酸）分别给出了最佳抑制反应。