Next Generation Virucides – Peptoids
Posted on June 11th, 2019
Maxwell Biosciences is developing a new class of potent, safe and biostable synthetic peptide-like small molecules currently in toxicology testing to treat common viral infections in humans.
Maxwell’s new drug class include multiple drug candidates are based on a oligoglycine backbone (similar to naturally occurring peptides), yet with a difference in their molecular structure side chains are appended to backbone nitrogens. Due to the stronger nitrogen bond, this novel peptoid (meaning “peptide-like”) synthetic virucides have been shown by multiple labs to be irreversibly inactivate viral DNA at low doses. Early preclinical data from indepedent labs also shows potential for safety. Maxwell’s lead virucidal peptoids are sequence- and chain-length specific, 6- to 13mer oligo-N-substituted glycines, designed to serve as structural, functional, and mechanistic mimics of natural virucidal peptides used by the human immune system to defend against all kinds of pathogens. This virucidal peptoid class is protected through 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 highly potent, 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.