Next Generation Virucides – Peptoids

Posted on June 11th, 2019

Maxwell Biosciences is developing a new class of potent, safe, biostable synthetic peptide-like small molecules currently in toxicology testing to treat common viral infections in humans. Read more about how peptoids mimic natural virucides.

Virucidal Peptoid

Maxwell’s new drug class includes multiple drug candidates based on naturally occurring immune peptides, but with side chains appended to backbone nitrogens instead of carbon. The nitrogen bond is stronger than a carbon bond, and these novel peptoid  (“peptide-like”) synthetic virucides have been shown to irreversibly inactivate viral DNA at low doses. Early preclinical data also shows  safety as a potential therapeutic for humans.

Novel, Patented Technology
Maxwell’s lead virucidal peptoids are designed to serve as structural, functional, and mechanistic mimics of natural virucidal peptides used by the human immune system to defend against pathogens. This virucidal peptoid class is protected by a granted patent assigned to Maxwell Biosciences by the US Department of Energy and US National Institutes of Health.

We have published the design, characterization, anti-infective activity, and biomimetic mechanisms of synthetic anti-infective peptoids in major peer-reviewed journals. Synthetic virucidal peptoids are synthesized at low cost on a robotic synthesizer and can be scaled up easily, with facile access to high chemical diversity. In their ease of synthesis, peptoids are unique among peptide mimetics. To identify our lead candidates (6mer-13mers), 70 different short synthetic anti-infective peptoids were synthesized, purified, and tested against viruses, 47 different bacterial microorganisms, including wild-type and drug-resistant variants. Many of our anti-infective peptoid drug candidates are as potent as well-known anti-infective drugs currently approved by the FDA (0.4-6.5 µM minimum inhibitory concentrations, MICs). The minimum inhibitory concentration is the smallest amount of a drug necessary to prevent visible growth of the pathogen. 

The biomimetic mechanism of action of anti-infective peptoids was shown using a wide range of biophysical tools, including studies of pathogen membranes and DNA, using scanning electron microscopy, transmission electron microscopy, and soft X-ray tomography of untreated vs. treated pathogens. We used super-resolution fluorescence microscopy to show that our lead drug candidates penetrate negatively charged membranes and cause rapid-onset solidification of negatively charged DNA and RNA; this mechanism is identical to that of the human peptide, the cathelicidin LL-37. Due to the mechanism of action, the likelihood of pathogenic resistance emerging to synthetic peptoid candidates may be less than that of conventional drugs, which have more specific molecular targets.

Dr Annelise Barron is the primary inventor and scientific co-founder of Maxwell Biosciences. Below is a list of the publications that have published her work as well as the work of other scientists who are building upon her research using Maxwell’s patented peptoid drug class. This data shows the advantages of using peptoids as broad spectrum anti-infectives and how peptoid anti-infectives mimic antimicrobial peptides.