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Antimicrobial Peptide-PNA Conjugates Selectively Targeting Bacterial Genes
Final rept. 1 Sep 2012-31 May 2013
NEW YORK UNIV NY
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As summarized in ARO Topic A09A-T004, resistance to antibiotics in current use continues to spread, while the pipeline of approved new antibiotics is shrinking. Antibiotic therapy today is a crude and increasingly ineffective weapon against infection. Current broad spectrum antibiotics notoriously stimulate the spread of resistance, and also open the way to secondary infections by MRSA and other pathogens. We offer here a solution that avoids stimulating resistance as well as collateral damage to the natural biome a target selective antimicrobial therapy. As a proof-of-concept project, this proposal seeks to explore the possibility that non-covalently linked combinations of peptide mimetics and peptide nucleic acids PNAs provide a basis for a strain-selective antibacterial therapy. Initial publications suggest that conjugates of cell penetrating peptides and PNA s can overcome the barrier in transporting the PNA s into cells. The strategy is to use RW4D and RW3, both designed in our lab, to guide a PNA sequence conjugated or not to the appropriate target RNA and thereby silence its expression. In initial testing, we used PNA sequences designed to inhibit growth of E. coli and MRSA cells, already reported in literature previously, but using our RW motif. Our preliminary results with this experiment are positive
APPROVED FOR PUBLIC RELEASE