Sotiropoulou Georgia, Zingkou Eleni, Bisyris Evangelos, Pampalakis Georgios
Department of Pharmacy, School of Health Sciences, University of Patras, 26500 Rion-Patras, Greece.
Department of Pharmacognosy-Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Pharmaceutics. 2022 Apr 30;14(5):977. doi: 10.3390/pharmaceutics14050977.
Proteases are important enzymes in health and disease. Their activities are regulated at multiple levels. In fact, proteases are synthesized as inactive proenzymes (zymogens) that are activated by proteolytic removal of their pro-peptide sequence and can remain active or their activity can be attenuated by complex formation with specific endogenous inhibitors or by limited proteolysis or degradation. Consequently, quite often, only a fraction of the protease molecules is in the active/functional form, thus, the abundance of a protease is not always linearly proportional to the (patho)physiological function(s). Therefore, assays to determine the active forms of proteases are needed, not only in research but also in molecular diagnosis and therapy. Activity-based probes (ABPs) are chemical entities that bind covalently to the active enzyme/protease. ABPs carry a detection tag to enable localization and quantification of specific enzymatic/proteolytic activities with applications in molecular imaging and diagnosis. Moreover, ABPs act as suicide inhibitors of proteases, which can be exploited for delineation of the functional role(s) of a given protease in (patho) biological context and as potential therapeutics. In this sense, ABPs represent new theranostic agents. We outline recent developments pertaining to ABPs for proteases with potential therapeutic applications, with the aim to highlight their importance in theranostics.
蛋白酶在健康和疾病中都是重要的酶。它们的活性在多个层面受到调控。事实上，蛋白酶最初是以无活性的酶原形式合成的，通过蛋白水解去除其前肽序列而被激活，之后可以保持活性，或者其活性可以通过与特定内源性抑制剂形成复合物、有限的蛋白水解或降解而减弱。因此，通常只有一部分蛋白酶分子处于活性/功能形式，所以，蛋白酶的丰度并不总是与（病理）生理功能呈线性比例关系。因此，不仅在研究中，而且在分子诊断和治疗中，都需要测定蛋白酶活性形式的方法。基于活性的探针（ABP）是能与活性酶/蛋白酶共价结合的化学实体。ABP带有一个检测标签，可用于在分子成像和诊断中对特定酶促/蛋白水解活性进行定位和定量。此外，ABP可作为蛋白酶的自杀性抑制剂，可用于在（病理）生物学背景下描绘特定蛋白酶的功能作用，并作为潜在的治疗药物。从这个意义上说，ABP代表了新的治疗诊断试剂。我们概述了具有潜在治疗应用的蛋白酶ABP的最新进展，旨在突出它们在治疗诊断中的重要性。
