Accession Number : ADA591768


Title :   Antimicrobial Peptide-PNA Conjugates Selectively Targeting Bacterial Genes


Descriptive Note : Final rept. 1 Sep 2012-31 May 2013


Corporate Author : NEW YORK UNIV NY


Personal Author(s) : Kallenbach, Neville R


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a591768.pdf


Report Date : 22 Jul 2013


Pagination or Media Count : 8


Abstract : 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 (RW)4D and (RW)3, 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!


Descriptors :   *ANTIMICROBIAL AGENTS , *BACTERIA , *GENES , *NUCLEIC ACIDS , *PEPTIDES , ANTIBIOTICS , BIOMIMETICS , CYSTEINE , RESISTANCE(BIOLOGY) , SYNTHESIS(CHEMISTRY)


Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Microbiology
      Pharmacology
      Organic Chemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE