Peptide foldamer-based inhibitors of the SARS-CoV-2 S protein-human ACE2 interaction.

Autor: Marković V; Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wrocław, Poland., Shaik JB; Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wrocław, Poland., Ożga K; Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wrocław, Poland., Ciesiołkiewicz A; Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wrocław, Poland., Lizandra Perez J; Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wrocław, Poland., Rudzińska-Szostak E; Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wrocław, Poland., Berlicki Ł; Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wrocław, Poland.
Jazyk: angličtina
Zdroj: Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2023 Dec; Vol. 38 (1), pp. 2244693.
DOI: 10.1080/14756366.2023.2244693
Abstrakt: The entry of the SARS-CoV-2 virus into a human host cell begins with the interaction between the viral spike protein (S protein) and human angiotensin-converting enzyme 2 (hACE2). Therefore, a possible strategy for the treatment of this infection is based on inhibiting the interaction of the two abovementioned proteins. Compounds that bind to the SARS-CoV-2 S protein at the interface with the alpha-1/alpha-2 helices of ACE2 PD Subdomain I are of particular interest. We present a stepwise optimisation of helical peptide foldamers containing trans -2-aminocylopentanecarboxylic acid residues as the folding-inducing unit. Four rounds of optimisation led to the discovery of an 18-amino-acid peptide with high affinity for the SARS-CoV-2 S protein ( K d = 650 nM) that inhibits this protein-protein interaction with IC 50 = 1.3 µM. Circular dichroism and nuclear magnetic resonance studies indicated the helical conformation of this peptide in solution.
Databáze: MEDLINE
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