Design of a PEGylated Antimicrobial Prodrug with Species-Specific Activation.

ABSTRACT: The rise of multidrug-resistant (MDR) "superbugs" has created an urgent need to develop new classes of antimicrobial agents to target these organisms. Oligothioetheramides (oligoTEAs) are a unique class of antimicrobial peptide (AMP) mimetics with one promising compound, BDT-4G, displaying potent activity against MDR Pseudomonas aeruginosa clinical isolates. Despite widely demonstrated potency, BDT-4G and other AMP mimetics have yet to enjoy broad preclinical success against systemic infections, primarily due to their cytotoxicity. In this work, we explore a prodrug strategy to render BDT-4G inactive until it is exposed to an enzyme secreted by the targeted bacteria. The prodrug consists of polyethylene glycol (PEG) conjugated to BDT-4G by a peptide substrate. PEG serves to inactiva

SUBMITTER: O'Leary MK 

PROVIDER: S-EPMC8270352 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature