De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein
Name
acscentsci.0c01309.pdf
Description
Published version
Size
3.35 MB
Format
Adobe PDF
Checksum (MD5)
1000dca13670de4fcce49bfd9cf7b51f
Author(s)
Pomplun, Sebastian Johannes
Jbara, Muhammad
Quartararo, Anthony James
Zhang, Genwei
Brown, Joseph S.
Lee, Yen-Chun
Ye, Xiyun
Hanna, Stephanie
Pentelute, Bradley L.
Date Issued
December 2020
Journal
ACS Central Science
Publisher
American Chemical Society (ACS)
Citation
Pomplun, Sebastian et al. "De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein." ACS Central Science 7, 1 (December 2020): 156–163 © 2020 American Chemical Society
Version
Final published version
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 Kd = 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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/acscentsci.0c01309
