Volume 5, 2022
Proteomics, Proteolysis and Amyloid beta
|Number of page(s)||11|
|Section||Life Sciences - Medicine|
|Published online||04 July 2022|
Realtime, continuous assessment of complex-mixture protease and protease inhibitor activity
Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
2 New Liberty Proteomics Corporation, New Liberty, KY 40355, USA
* Corresponding author: email@example.com
Accepted: 18 May 2022
Recently the treatment PAXLOVID™ (nirmatrelvir co-packaged with ritonavir) was authorized for use as a treatment for COVID-19. The presumed mechanism of action of the treatment, an inhibitor of a Sars-Cov-2 “3CL” protease, continues decades-long interest in viral protease inhibition in the fight against pathogenic viruses (e.g., HIV protease inhibitors). Proteolysis assay methods vary widely, roughly bounded by interrogation of basic biochemistry and high-throughput, early-stage drug screening. Reported here are methods that provide unique and biologically relevant characterization of proteolysis and protease inhibition. A companion report provides evidence that these methods show promise for drug and basic biological discovery, especially for early detection of potential side effects. Electron spin resonance spectroscopy and spin labeling (ESRSL) of whole proteins are leveraged to monitor reactants and products of whole-protein digestion through differentiation of angular mobility of those products and reactants. These proof-of-concept data demonstrate consistency with prior art for all possible combinations of four proteases, two whole-protein substrates and three inhibitors. Thus, ESRSL is shown to uniquely and widely interrogate proteolysis of natural, whole-protein, substrates insuring the biological relevance of results.
Key words: Proteomics / Methodology / Proteolysis
© S.-E. Leonard et al., Published by EDP Sciences, 2022
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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