Inhibition of aminopeptidases N, A and W. A re-evaluation of the actions of bestatin and inhibitors of angiotensin converting enzyme.
Inhibition of aminopeptidases N, A and W. A re-evaluation of the actions of bestatin and inhibitors of angiotensin converting enzyme.
复制标题
DOI：
10.1016/0006-2952(92)90065-q
复制
发表时间：
1992-11-03
影响因子：
5.8
通讯作者：
Hooper NM
中科院分区：
文献类型：
--
作者：
Tieku S;Hooper NM
直接比较了一系列金属肽酶抑制剂对猪肾细胞表面锌氨肽酶、氨肽酶A（AP-A; EC 3.4.11.2）、氨肽酶N（AP-N; EC 3.4.11.7）和氨肽酶W（AP-W; EC 3.4.11.16）活性的影响。Amastatin和probestin对所有三种氨肽酶都有效，在低微摩尔范围（I50 = 1.5-20 μM）内引起50%抑制（I50）所需的抑制剂浓度（I50），除了probestin与AP-N显示的I50为50 nM。肌动蛋白不能显著抑制AP-A或AP-W，因此可以认为是相对选择性的抑制剂（I 50 = 2.0 μM AP-N）。相比之下，bestatin是一种相对较差的AP-N抑制剂（I50 = 89 μM），不能抑制AP-A，但对AP-W更有效（I50 = 7.9 μM）。因此，一些观察到的bestatin的化疗作用可能是由于抑制细胞表面AP-W。许多其他金属肽酶抑制剂，包括内肽酶-24.11（EC 3.4.24.11）和膜二肽酶（EC 3.4.13.11）的抑制剂，以及血管紧张素转化酶的羧烷基和磷酰基抑制剂（EC 3.4.15.1），均不能显著抑制AP-A、AP-N或AP-W。然而，巯基转化酶抑制剂伦替普利（I50 = 1.6 μM）、佐芬普利拉（I50 = 7.0 μM）和YS 980（I50 = 17.7 μM）可抑制AP-W，其I50值在微摩尔范围内。AP-A和AP-N均不受这些巯基化合物的影响。AP-W的抑制可能是巯基转化酶抑制剂临床应用中出现的一些副作用的原因。对AP-W完全选择性超过任何其他哺乳动物细胞表面锌氨肽酶的化合物的可用性可有助于鉴定内源性底物，从而鉴定AP-W的生理或病理生理作用。
The effects of a range of metallopeptidase inhibitors on the activities of the porcine kidney cell surface zinc aminopeptidases, aminopeptidase A (AP-A; EC 3.4.11.2), aminopeptidase N (AP-N; EC 3.4.11.7) and aminopeptidase W (AP-W; EC 3.4.11.16), have been directly compared. Amastatin and probestin were effective against all three aminopeptidases, with the concentration of inhibitor required to cause 50% inhibition (I50) in the low micromolar range (I50 = 1.5–20 μM), except for probestin with AP-N which displayed an I50 of 50 nM. Actinonin failed to inhibit significantly either AP-A or AP-W, and thus can be considered a relatively selective inhibitor (I50 = 2.0 μM of AP-N. In contrast, bestatin was a relatively poor inhibitor of AP-N (I50 = 89 μm) and failed to inhibit AP-A, but was more potent towards AP-W (I50 = 7.9 μM). Thus, some of the observed chemotherapeutic actions of bestatin may be due to inhibition of cell-surface AP-W. A number of other metallopeptidase inhibitors, including inhibitors of endopeptidase-24.11 (EC 3.4.24.11) and membrane dipeptidase (EC 3.4.13.11), and the carboxylalkyl and phosphoryl inhibitors of angiotensin converting enzyme (EC 3.4.15.1) failed to inhibit significantly AP-A, AP-N or AP-W. However, AP-W was inhibited with I50 values in the micromolar range by the sulphydryl converting enzyme inhibitors rentiapril (I50 = 1.6 μM), zofenoprilat (I50 = 7.0 μM) and YS 980 (I50 = 17.7 μM). Neither AP-A nor AP-N were affected by these sulphydryl compounds. Inhibition of AP-W may account for some of the side effects noted with the clinical use of the sulphydryl converting enzyme inhibitors. The availability of compounds which are totally selective for AP-W over any of the other mammalian cell surface zinc aminopeptidases may aid in identifying endogenous substrates, and thus physiological or pathophysiological role(s) of AP-W.
登录
查看更多内容
影响因子：
4.1
作者：
GEE, NS;KENNY, AJ
通讯作者：
KENNY, AJ
影响因子：
3
作者：
MANCIA, G
通讯作者：
MANCIA, G
影响因子：
5.8
作者：
PALMIERI, FE;BAUSBACK, HH;WARD, PE
通讯作者：
WARD, PE
氨基肽酶N是肠道病毒冠状病毒TGEV的主要受体。
影响因子：
64.8
作者：
Delmas B;Gelfi J;L'Haridon R;Vogel LK;Sjöström H;Norén O;Laude H
通讯作者：
Laude H
DOI：
10.1016/0005-2744(70)90058-6
发表时间：
1970-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
NAGATSU, I;NAGATSU, T;MEHL, JW
通讯作者：
MEHL, JW