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
Abstract The β-coronavirus SARS-CoV-2 has caused a global pandemic. Affinity reagents targeting the SARS-CoV-2 spike protein, the most exposed surface structure of the virus, 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 to 970 nM) for RBD and selectivity over human serum proteins. Picomolar RBD concentrations in biological matrix could be detected using the biotinylated lead peptide in ELISA format. These peptides might associate with the SARS-CoV-2-spike-RBD at a site unrelated to ACE2 binding, making them potential orthogonal reagents for sandwich immunoassays. We envision our discovery as a robust starting point for the development of SARS-CoV-2 diagnostics or conjugates for virus directed delivery of therapeutics. biorxiv;2020.09.29.317131v1/UFIG1F1ufig1
Ye Xiyun、Jbara Muhammad、Pomplun Sebastian、Quartararo Anthony J.、Pentelute Bradley L.、Lee Yen-Chun、Brown Joseph S.、Hanna Stephanie、Zhang Genwei
Massachusetts Institute of Technology, Department of ChemistryMassachusetts Institute of Technology, Department of ChemistryMassachusetts Institute of Technology, Department of ChemistryMassachusetts Institute of Technology, Department of ChemistryMassachusetts Institute of Technology, Department of Chemistry||The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology||Center for Environmental Health Sciences, Massachusetts Institute of Technology||Broad Institute of MIT and HarvardMassachusetts Institute of Technology, Department of ChemistryMassachusetts Institute of Technology, Department of ChemistryMassachusetts Institute of Technology, Department of ChemistryMassachusetts Institute of Technology, Department of Chemistry
生物科学研究方法、生物科学研究技术基础医学微生物学
Ye Xiyun,Jbara Muhammad,Pomplun Sebastian,Quartararo Anthony J.,Pentelute Bradley L.,Lee Yen-Chun,Brown Joseph S.,Hanna Stephanie,Zhang Genwei.De Novo Discovery of High Affinity Peptide Binders for the SARS-CoV-2 Spike Protein[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2020.09.29.317131.点此复制
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