Engineering natural peptides for discovery of
novel anti-infectives
Peptoids are a unique class of peptidomimetics based on oligo-N-substituted glycine backbone. As a biomimetic material, the properties of peptoids lie in-between natural biopolymers and non-natural synthetic polymers, exhibiting key features that are unique in natural proteins such as programmability at the monomer level and sequence specificity. The structural similarity to polypeptides has been responsible for the impressive diversity of conformation and biological activity observed for peptoids; however, non-natural N-substituents render them higher stability than that of natural counterpart (i.e., protease-stable). Given the unique structural properties, the potential applications of peptoid are widely open in various fields including biomedicine and material sciences.
In this presentation our ongoing efforts to mimic natural peptides or proteins using peptoids and to discover novel anti-infective agents will be introduced. One of the most actively investigated field in the peptoid community is the mimicry of natural antimicrobial peptides and cell-penetrating peptides. Recent discovery of amphipathic peptoids in our lab with potent antimicrobial activity including multi-drug resistant (MDR) pathogens and enhanced selectivity will be presented. With sequence and helicity modulation of the amphipathic peptoids, subcellular organ targeting vehicle with excellent efficiency was identified, and their biomedical applications will be introduced. Finally, synthesis and structural investigation of macrocyclic peptides based on natural peptides with potent anti-infective activity will be presented.
