Document Type

Restricted

Advisor

Tanya Schneider

Publication Date

2026

Abstract

2. Abstract Antibiotic resistance continues to pose a serious threat to public health, and the discovery of new molecular scaffolds has not kept pace in addressing these needs. Particularly for the highly resistant Gram-negative Pseudomonas aeruginosa, new targets need to be explored, which has prompted efforts in designing quorum-sensing (QS) inhibitors that can shut off QS pathways implicated in biofilm formation, virulence factor production, and ultimately antibiotic resistance. QS in P. aeruginosa consists of two cooperative systems, Las and Rhl. LasR is the transcription factor that regulates both of these systems and influences the progression of QS, which therefore makes this protein an ideal candidate for QS inhibition. One strategy for inhibiting QS, employed in this study, is to synthesize protein-protein interaction (PPI) inhibitors that bind to specific protein interfaces and prevent secondary protein interactions. In this thesis, three novel ɑ-helix mimetics were synthesized in continuation of the previously synthesized molecules from the Schneider lab, demonstrating anti-LasR activity. This work progressed our understanding of the functional groups necessary for maintaining antagonistic behaviors towards LasR and mimicking the binding of the natural inhibitor QsIA.

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The views expressed in this paper are solely those of the author.