(a) Conjugated oligoelectrolytes (COEs) share a modular structure that spontaneously integrates into the bacterial membrane. (b) Illustration of different COE structural modules. (c) Specific example: COE2-2hexyl.
The goals of this project are to (a) interface with Army colleagues at WRAIR so that COEs can be tested against a range of pathogens of relevance to the Army and its personnel, (b) determine the mechanism of drug action and resistance, and (c) examine how the structural modalities available for molecular design affect efficacy, toxicity, and drug resistance. It is worth highlighting that COEs have no structural relationship to any known antibiotic. These studies may therefore yield the first fundamentally new class of broad-spectrum antibiotics in fifty years. COE synthesis is relatively cheap and easy to scale up compared to conventional antibiotics, with minimal decomposition even after years in solid or solution form without refrigeration. Up to now, all of the advances have been through intuition. This ICB study program is the first mechanism-based and Army-integrated effort in this area of basic science.