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Discovering Peptide Inhibitors of the Spike Protein and Human ACE2 Receptor Interaction via Competitive Elution in Phage Display

Thesis advisor: Jianman Gao / The interaction between the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the human angiotensin-converting enzyme 2 (hACE2) receptor is an advantageous target for the development of therapies for COVID-19. We used an anti spike receptor binding domain (S RBD) antibody (AM122) to competitively elute phage binding to the S RBD in phage display screening to identify a novel peptide that binds the S protein and hACE2 interaction. We identified a peptide sequence (P1: CPLEYHTC) as a possible hit, and the KD was determined to be 2.667 μM, indicating the potential of this peptide sequence as a therapeutic agent. However, we found no inhibition of the spike protein and hACE2 receptor interaction, suggesting that the peptide may not directly bind to the hACE2 binding site on S RBD. Although further studies are needed, the competitive elution method in phage display screening appears to be an effective method for elucidating onsite peptide sequences that target protein-protein interactions (PPIs). / Thesis (BA) — Boston College, 2023. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Departmental Honors. / Discipline: Chemistry.

Identiferoai:union.ndltd.org:BOSTON/oai:dlib.bc.edu:bc-ir_109750
Date January 2023
CreatorsWei, Nicole
PublisherBoston College
Source SetsBoston College
LanguageEnglish
Detected LanguageEnglish
TypeText, thesis
Formatelectronic, application/pdf
RightsCopyright is held by the author, with all rights reserved, unless otherwise noted.

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