A Short Peptide Inhibitor as an Activity-Based Probe for Matriptase-2

被引：7

作者：

Mangold, Martin ^{[1
]}

Guetschow, Michael ^{[1
]}

Stirnberg, Marit ^{[1
]}

机构：

[1] Univ Bonn, Inst Pharmaceut, Pharmaceut Chem 1, D-53113 Bonn, Germany

来源：

PHARMACEUTICALS | 2018年 / 11卷 / 02期

关键词：

matriptase-2; Activity-based probe; peptide inhibitor; IRON OVERLOAD; CHLOROMETHYL KETONE; BETA-THALASSEMIA; CLEAVAGE SITES; TMPRSS6; PROTEASE; BINDING; IDENTIFICATION; HEPCIDIN; TRYPSIN;

D O I：

10.3390/ph11020049

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Matriptase-2 is a type II transmembrane serine protease and a key regulator of systemic iron homeostasis. Since the activation mechanism and several features of the physiological role of matriptase-2 are not fully understood, there is strong need for analytical tools to perform tasks such as distinguishing active and inactive matriptase-2. For this purpose we present a short biotinylated peptide derivative with a chloromethyl ketone group, biotin-RQRR-CMK, as an activity-based probe for matriptase-2. Biotin-RQRR-CMK was kinetically characterized and exhibited a second-order rate constant of inactivation (k(inac)/K-i) of 10,800 M-1 s(-1) towards the matriptase-2 activity in the supernatant of transfected human embryonic kidney (HEK) cells. Biotin-RQRR-CMK was able to label active matriptase-2, as visualized in western blot experiments. Pretreatment with aprotinin, an active-site directed inhibitor of serine proteases, protected matriptase-2 from the reaction with biotin-RQRR-CMK.

引用

页数：10

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