Citation

Sotiropoulou G, Zingkou E, Bisyris E, Pampalakis G. Pharmaceutics 2022; 14(5).

Copyright

(Copyright © 2022, MDPI: Multidisciplinary Digital Publications Institute)

DOI

10.3390/pharmaceutics14050977

PMID

unavailable

Abstract

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 acti-vated 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 proteol-ysis 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 pro-teases, 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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Language: en

Keywords

human; Review; conceptual framework; mass spectrometry; radiopharmaceutical agent; unclassified drug; atherosclerosis; nonhuman; enzyme activity; phage display; prostate cancer; protein degradation; proteinase; chemical structure; quantitative analysis; enzyme specificity; protein function; structure analysis; enzyme linked immunosorbent assay; epoxide; contrast medium; serine proteinase; peptidase; fluorescent dye; molecular imaging; molecular diagnosis; malignant neoplasm; NETosis; chemical modification; activity based probe; activity-based probes (ABPs); activography; cathepsin; cathepsins; click chemistry; combinatorial library; enzyme localization; kallikrein related peptidase; kallikrein-related peptidases (KLKs); ketone derivative; leukocyte elastase; phos-phonates; phosphonic acid derivative; proteases; theranostic nanomedicine; theranostics