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2 2022

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Nienaturalne aminokwasy jako strategia do otrzymywania substratów, inhibitorów i niskocząsteczkowych sond aktywności dla enzymów proteolitycznych

Poręba Marcin, Kasperkiewicz-Wasilewska Paulina, Rut Wioletta, Drąg Marcin

Wiadomości Chemiczne

2022

[Z] 76, 5-6

433--454

Proteolytic enzymes are molecular scissors that are responsible for the amide bond breakdown in peptide and protein substrates. Over the years, the view on proteases has been considerably changed from non-specific digestive enzymes to sophisticated biocatalysts, which by performing limited proteolysis control virtually all biological processes. In order to better understand how proteases work and what are their biologically relevant target substrates, it is indispensable to determine their catalytic preferences. This knowledge can be further utilized to develop selective substrates, inhibitors and activity-based probes (ABPs) enabling the monitoring of proteases activity in various settings, from in vitro analysis on recombinant enzymes or cell lysates to ex vivo and in vivo imaging at the single cell level. Among many chemical-based approaches that have been developed and applied over the years, the Hybrid Combinatorial Substrate Library (HyCoSuL) technology has emerged as one of the most powerful one. HyCoSuL is a combinatorial peptide-based library of fluorogenic substrates, that comprise natural and unnatural amino acids, that can deeply explore the chemical space in proteases active site, providing a structural framework for the development of highly-selective chemical tools. In this review we present the most prominent examples of proteolytic enzymes that have been profiled with HyCoSuL approach yielding selective substrates, potent inhibitors, and very sensitive activity-based probes.

Monitorowanie aktywności proteolitycznej jako element diagnostyki chorób cywilizacyjnych

Gruba Natalia, Romanowska Anita, Rejmak Wiktoria, Sikora Honorata, Wysocka Magdalena, Lesner Adam

Wiadomości Chemiczne

2022

[Z] 76, 5-6

335--347

Proteolytic enzymes are essential for the proper functioning of every living cell. Due to their great importance in controlling metabolic changes in living organisms, they could be used in the diagnosis of civilization diseases. Hence, the search for new methods of determining and controlling their activity is extremely important. Our team, has been studying substrates of proteases and their potential use in detection of biomarkers activity for many years.