González-Muñiz R, Harto J R, de Ceballos M L, del Río J, García-López M T
Instituto de Química Médica, Madrid, Spain.
Arch Pharm (Weinheim). 1992 Dec;325(12):743-9. doi: 10.1002/ardp.19923251202.
With the aim of increasing the inhibitory potency of the analgesic dipeptide H-Trp(Nps)-Lys-OMe against enkephalin-degrading aminopeptidases, the following derivatives bearing chelating groups at the N-terminus have been synthesized: Ac-Trp(Nps)-Lys-OMe (3), HS(CH2)nCO-Trp(Nps)-Lys-OMe [n = 1 (4), n = 2 (5)], MeOCO(CH2)n-Trp(Nps)-Lys-OMe [n = 1 (6), n = 2 (7)] and analogues in which the N alpha-amino group has been replaced by a methoxycarbonyl group (8) and a bidentate hydroxamate function (9), respectively. The inhibitory activities of all these compounds and the S-protected derivatives EtNHCOS(CH2)nCO-Trp(Nps)-Lys-OMe [n = 1 (16), n = (17)] against the mentioned enzyme, isolated from rat striatum, are compared with those of the parent dipeptide 2 and bestatin. All the new derivatives showed, in general, inhibitory potencies of the same order of magnitude as compound 2.
为了提高镇痛二肽H-Trp(Nps)-Lys-OMe对脑啡肽降解氨基肽酶的抑制效力，已合成了以下在N端带有螯合基团的衍生物：Ac-Trp(Nps)-Lys-OMe（3）、HS(CH2)nCO-Trp(Nps)-Lys-OMe[n = 1（4），n = 2（5）]、MeOCO(CH2)n-Trp(Nps)-Lys-OMe[n = 1（6），n = 2（7）]以及Nα-氨基分别被甲氧基羰基（8）和双齿异羟肟酸酯官能团（9）取代的类似物。将所有这些化合物以及S-保护衍生物EtNHCOS(CH2)nCO-Trp(Nps)-Lys-OMe[n = 1（16），n =（17）]对从大鼠纹状体分离出的上述酶的抑制活性与母体二肽2和贝司他汀的抑制活性进行了比较。总体而言，所有新衍生物的抑制效力与化合物2处于同一数量级。
