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

被引：8

作者：

Markovic, Violeta ^{[1
]}

Shaik, Jeelan Basha ^{[1
]}

Ozga, Katarzyna ^{[1
]}

Ciesiolkiewicz, Agnieszka ^{[1
]}

Lizandra Perez, Juan ^{[1
]}

Rudzinska-Szostak, Ewa ^{[1
]}

Berlicki, Lukasz ^{[1
]}

机构：

[1] Wroclaw Univ Sci & Technol, Dept Bioorgan Chem, Wroclaw, Poland

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2023年 / 38卷 / 01期

关键词：

COVID-19; foldamers; peptides; helix; protein-protein interaction; BLI; RECEPTOR-BINDING DOMAIN; HELICAL SECONDARY STRUCTURES; ALPHA/BETA-PEPTIDES; BETA-PEPTIDES; HIGH-AFFINITY; CRYSTALLOGRAPHIC CHARACTERIZATION; FOLDING PROPENSITY; MIMICRY; CELL; DISCOVERY;

D O I：

10.1080/14756366.2023.2244693

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 IC50 = 1.3 & mu;M. Circular dichroism and nuclear magnetic resonance studies indicated the helical conformation of this peptide in solution.

引用

页数：12

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