Gomes M D, Juliano L, Ferro E S, Matsueda R, Camargo A C
Department of Pharmacology, Institute of Biomedical Sciences, USP, São Paulo, Brazil.
Biochem Biophys Res Commun. 1993 Dec 15;197(2):501-7. doi: 10.1006/bbrc.1993.2507.
Brain endo-oligopeptidase A, a neuropeptide-metabolizing endopeptidase, has been considered a cysteine-endopeptidase because it is activated by thiols and inhibited by phydroxymercuribenzoate or 5,5'-dithiobis-(2-nitrobenzoic acid). The understanding of the unique specificity of endo-oligopeptidase A was useful for the synthesis of affinity labeling compounds containing as a thiol reactive group the Cys-(3-nitro-2-pyridinesulfenyl) group into dynorphin-derived peptides which are among the best substrates and competitive inhibitor of endopeptidase 22.19. Of the ten compounds tested, only peptides containing 8 to 13 amino acid residues caused irreversible inhibition. The fact that the most effective inhibitors had the reactive group either at the P'1 or at P'3 position [nomenclature of Schechter and Berger] would seem to argue that the reactive cysteine is in the vicinity of the active site, or actually involved in the catalytic step.
脑内寡肽酶A是一种代谢神经肽的内肽酶，一直被认为是一种半胱氨酸内肽酶，因为它可被硫醇激活，并被对羟基汞苯甲酸或5,5'-二硫代双（2-硝基苯甲酸）抑制。对寡肽酶A独特特异性的了解有助于合成亲和标记化合物，该化合物将半胱氨酸-（3-硝基-2-吡啶亚磺酰基）基团作为硫醇反应基团引入强啡肽衍生肽中，这些肽是内肽酶24.19的最佳底物和竞争性抑制剂之一。在测试的十种化合物中，只有含有8至13个氨基酸残基的肽会导致不可逆抑制。最有效的抑制剂在P'1或P'3位置[谢克特和伯杰命名法]具有反应基团这一事实似乎表明，反应性半胱氨酸在活性位点附近，或实际上参与了催化步骤。
