tetano
Editor, Senior Moderator
ACS Cent Sci
. 2021 Jan 27;7(1):156-163.
doi: 10.1021/acscentsci.0c01309. Epub 2020 Dec 18.
De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein
Sebastian Pomplun[SUP] 1 [/SUP], Muhammad Jbara[SUP] 1 [/SUP], Anthony J Quartararo[SUP] 1 [/SUP], Genwei Zhang[SUP] 1 [/SUP], Joseph S Brown[SUP] 1 [/SUP], Yen-Chun Lee[SUP] 1 [/SUP], Xiyun Ye[SUP] 1 [/SUP], Stephanie Hanna[SUP] 1 [/SUP], Bradley L Pentelute[SUP] 1 2 3 4 [/SUP]
Affiliations
Abstract
The β-coronavirus SARS-CoV-2 has caused a global pandemic. Affinity reagents targeting the SARS-CoV-2 spike protein are of interest for the development of therapeutics and diagnostics. We used affinity selection-mass spectrometry for the rapid discovery of synthetic high-affinity peptide binders for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. From library screening with 800 million synthetic peptides, we identified three sequences with nanomolar affinities (dissociation constants K [SUB]d[/SUB] = 80-970 nM) for RBD and selectivity over human serum proteins. Nanomolar RBD concentrations in a biological matrix could be detected using the biotinylated lead peptide in ELISA format. These peptides do not compete for ACE2 binding, and their site of interaction on the SARS-CoV-2-spike-RBD might be unrelated to the ACE2 binding site, making them potential orthogonal reagents for sandwich immunoassays. These findings serve as a starting point for the development of SARS-CoV-2 diagnostics or conjugates for virus-directed delivery of therapeutics.
. 2021 Jan 27;7(1):156-163.
doi: 10.1021/acscentsci.0c01309. Epub 2020 Dec 18.
De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein
Sebastian Pomplun[SUP] 1 [/SUP], Muhammad Jbara[SUP] 1 [/SUP], Anthony J Quartararo[SUP] 1 [/SUP], Genwei Zhang[SUP] 1 [/SUP], Joseph S Brown[SUP] 1 [/SUP], Yen-Chun Lee[SUP] 1 [/SUP], Xiyun Ye[SUP] 1 [/SUP], Stephanie Hanna[SUP] 1 [/SUP], Bradley L Pentelute[SUP] 1 2 3 4 [/SUP]
Affiliations
- PMID: 33527085
- PMCID: PMC7755081
- DOI: 10.1021/acscentsci.0c01309
Abstract
The β-coronavirus SARS-CoV-2 has caused a global pandemic. Affinity reagents targeting the SARS-CoV-2 spike protein are of interest for the development of therapeutics and diagnostics. We used affinity selection-mass spectrometry for the rapid discovery of synthetic high-affinity peptide binders for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. From library screening with 800 million synthetic peptides, we identified three sequences with nanomolar affinities (dissociation constants K [SUB]d[/SUB] = 80-970 nM) for RBD and selectivity over human serum proteins. Nanomolar RBD concentrations in a biological matrix could be detected using the biotinylated lead peptide in ELISA format. These peptides do not compete for ACE2 binding, and their site of interaction on the SARS-CoV-2-spike-RBD might be unrelated to the ACE2 binding site, making them potential orthogonal reagents for sandwich immunoassays. These findings serve as a starting point for the development of SARS-CoV-2 diagnostics or conjugates for virus-directed delivery of therapeutics.