Michael A. Bertucci
Talk Session: SESSION 8: PEPTIDE- AND PROTEIN-BASED THERAPEUTICS
Date: Tuesday, June 14, 2022
Talk Time: 08:00 am – 08:25 am
Talk Title: Designing Peptide-Based Quorum Sensing Modulators for Bacterial Pathogens
Michael graduated from Stevens Institute of Technology with B.S. in Chemical Biology before pursuing his Ph.D. in Chemistry as a Venable Fellow at the University of North Carolina at Chapel Hill. Under the mentorship of Dr. Michel R. Gagné, he investigated methods for derivitizing N-Acyl Homoserine Lactone (AHLs), key signaling molecules in gram-negative bacterial quorum sensing. He joined the chemistry department at Hartwick College as a Visiting Assistant Professor in 2014 before moving to Moravian University one year later. While at Moravian, he has taught Organic Chemistry I & II, Bioorganic & Medicinal Chemistry, Synthetic Organic Chemistry and Senior Seminar for Chemistry and Biochemistry Majors. In 2021, he accepted an offer to join the chemistry department at his current institution, Lafayette College.
Quorum sensing is a mechanism of density-dependent chemical communication by which bacteria regulate group function. In the opportunistic pathogens Streptococcus pneumoniae and Bacillus cereus, the quorum sensing systems are regulated by the peptides CSP and PapR respectively. Through iterative structure-activities studies, we remodeled the hydrophobic binding face of CSP1 using non-proteogenic amino acids that enhanced binding of the peptide to its cognate receptor (ComD1) while increasing proteolytic stability. By incorporating N-methyl amino acids and C-terminal modifications into the PapR7 scaffold, we were able to develop potent QS inhibitors for B. cereus, drastically reducing hemolytic activity in in vitro assays.