Antimicrobial Dendrimeric Peptides and Triazine Compounds
Neville Kallenbach, Ph.D.
Professor, Department of Chemistry
Background and Description of Technology:
A wide range of antimicrobial peptides is secreted in plants and animals to challenge attack by foreign viruses, bacteria or fungi. These cationic antimicrobial peptides have been considered as prospective antibiotics agents because their effect is rapid, broad spectrum and indifferent to resistance to standard antibiotics. However, their success thus far has been limited, likely due to the requirement that they be present in a fairly high concentration to achieve killing and that such high concentrations are believed to exert a potentially cytotoxic effect on human erythrocytes, along with other cells and tissues.
Dr. Kallenbach has developed 2 families of molecules as novel antimicrobial agents:
Antimicrobial Dendrimeric Peptides: Pairs of specific amino acids from naturally occurring, antimicrobial peptides have been shown to represent the active pharmacophore responsible for antimicrobial activity. Dendrimers linking several groups of these amino acids produced potent antimicrobial agents with broad-spectrum activity against multidrug-resistant strains, sharply reduced cytotoxicity, and resistance to proteases. Drug resistance to these compounds has been demonstrated to develop far more slowly than standard antibiotics and in vitro studies have been conducted against several bacterial strains, including MRSA and A. baumannii. They also are effective in destroying bacteria in biofilms.
Antimicrobial Triazine Compounds: Using triazine based combinatorial chemistry, and the tool of quantitative structure-activity relationship, small, peptidomimetic molecules have been designed to match the pharmacophore and share the antimicrobial mechanism of AMPs. One of these candidates demonstrated an MIC50 of about 20μM against A. baumannii, B. anthracis, and S. aureus and was not highly hemolytic even at much higher concentrations.
Patent applications have been filed on the above technologies. NYU is seeking commercial partners to develop antimicrobials for topical and systemic uses as well as coating of surgical/medical equipment and surfaces to prevent microbial contamination and biofilms.