Linear and cyclic peptoids as potent antimicrobial agents
Associate Professor, Department of Chemistry
Background and Description of Technology:
The development of antibiotic resistance by bacterial pathogens is a growing public health threat and there is a significant market demand for novel antibiotics, particularly agents that exhibit new mechanisms of action to deter resistance as well as target emerging drug-resistant strains for which few therapeutic options are available. Oligomers of N-substituted glycine or peptoids, are an important class of peptidomimetics capable of forming stable secondary structures resistant to proteolytic degradation. Peptoids are a class of compounds with potential therapeutic applications having diverse biological activities and can be designed to display chemical moieties analogous to bioactive peptide side chains.
Dr. Kirshenbaum has identified a series of linear and cyclic cationic peptoids that are potent and selective antimicrobials. These agents mimic the function of naturally occurring antimicrobial peptides act by perturbing bacterial membranes. The optimized peptoid sequences are non-hemolytic and show antimicrobial activity against both gram- positive and gram-negative bacteria such as E. coli, B. subtilis and S. aureus including Methicillin-Sensitive and Methicillin-Resistant clinical isolates (MSSA and MRSA) Dr. Kirshenbaumʼs group has optimized the synthesis where it is rapid and high yielding.
Peptoids may serve as particularly effective anti-infective agents with minimal toxicity. They can be prepared as pharmaceutical compositions with efficacy that is rapid and broad spectrum. Moreover, their mechanism of action is a promising strategy for developing novel therapeutics, as pathogenic bacteria may be incapable of significantly altering the characteristics of their membrane components to establish resistance.
Patent applications have been filed covering a broad range of linear and cyclic peptoids with demonstrated activity against gram-negative and gram-positive applications. NYU is commercial partners to develop peptoid antimicrobials for the antibiotic market.