Rapid de novo discovery of peptidomimetic affinity reagents for human angiotensin converting enzyme 2
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s42004-022-00625-3.pdf
Description
Published version
Size
3.78 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Zhang, Genwei
Brown, Joseph S
Quartararo, Anthony J
Li, Chengxi
Tan, Xuyu
Hanna, Stephanie
Antilla, Sarah
Cowfer, Amanda E
Loas, Andrei
Pentelute, Bradley L
Date Issued
December 2022
Journal
Communications Chemistry
Publisher
Springer Science and Business Media LLC
Citation
Zhang, Genwei, Brown, Joseph S, Quartararo, Anthony J, Li, Chengxi, Tan, Xuyu et al. 2022. "Rapid de novo discovery of peptidomimetic affinity reagents for human angiotensin converting enzyme 2." Communications Chemistry, 5 (1).
Version
Final published version
Abstract
AbstractRapid discovery and development of serum-stable, selective, and high affinity peptide-based binders to protein targets are challenging. Angiotensin converting enzyme 2 (ACE2) has recently been identified as a cardiovascular disease biomarker and the primary receptor utilized by the severe acute respiratory syndrome coronavirus 2. In this study, we report the discovery of high affinity peptidomimetic binders to ACE2 via affinity selection-mass spectrometry (AS-MS). Multiple high affinity ACE2-binding peptides (ABP) were identified by selection from canonical and noncanonical peptidomimetic libraries containing 200 million members (dissociation constant, KD = 19–123 nM). The most potent noncanonical ACE2 peptide binder, ABP N1 (KD = 19 nM), showed enhanced serum stability in comparison with the most potent canonical binder, ABP C7 (KD = 26 nM). Picomolar to low nanomolar ACE2 concentrations in human serum were detected selectively using ABP N1 in an enzyme-linked immunosorbent assay. The discovery of serum-stable noncanonical peptidomimetics like ABP N1 from a single-pass selection demonstrates the utility of advanced AS-MS for accelerated development of affinity reagents to protein targets.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Center for Environmental Health Sciences
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s42004-022-00625-3
