Rationally-designed, D-conformation Antimicrobial Peptides as Novel Antibacterial Drug Candidates for the Treatment of Multi-drug-resistant Bacterial

Antimicrobial resistance is among the most challenging problems in microbiology and clinical medicine, and the DOD has seen a dramatic increase of resistant strains of MRSA and multi-drug-resistant Acinetobacter baumanii (MDR-AB) emerging in combat- and non-combat-related healthcare settings. Virulent/MDR infections are developing single/ multiple routes of resistance to the thirteen classes of currently available antiobiotics. New drugs now in trials hold little promise for major advances. Our BioAMPS/U. of Colorado STTR team proposes to pursue the much needed next-generation solution. We have developed a portfolio of alpha-helical antimicrobial peptides that exhibit broad-spectrum in vitro activity, and in Phase I we intend to prove the feasibility of identifying one or more lead peptide compounds that will function as effective antibacterials against MDR infections. Our novel, proprietary peptides target only the cytoplasmic membrane and do not require an interaction with a stereoselective receptor or pathway—an advantage that holds great potential for eliminating development of resistance. In Phase I we will screen three structurally unique series (13 analogs) of our peptides against 15 strains/isolates of MRSA and MDR-AB obtained from throughout the world to identify one or more novel antibacterial drug candidates for follow-on development in a larger Phase II STTR project.