Pentelute Lab MIT | De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein
The Pentelute Lab aims to invent new chemistry for the efficient and selective modification of proteins, to ‘hijack’ these biological machines for efficient drug delivery into cells and to create new machines to rapidly and efficiently manufacture peptides and proteins.
Pentelute Lab, Chemistry, MIT, Chemistry Department, Boston, Cambridge, Biology, Peptides, Peptide, Proteins, Science, Rapid, Brad Pentelute, Brad,
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De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein

De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein

ACS Cent. Sci. 2021, 7, 1, 156–163 Publication Date:December 17, 2020 https://doi.org/10.1021/acscentsci.0c01309
Sebastian Pomplun, Muhammad Jbara, Anthony J. Quartararo, Genwei Zhang, Joseph S. Brown, Yen-Chun Lee, Xiyun Ye, Stephanie Hanna, and Bradley L. Pentelute

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.

Category
2021, Publications