Peptides as Tools to Develop Novel Therapeutics and Soft Materials

Manish Nepal, Purdue University

Abstract

In recent years, peptides have attracted increased attention as a platform to develop next generation therapeutics. Herein, we discuss our efforts that involve applications of peptides to develop novel antibacterial agents and soft materials. First, we present a metal promoted self-assembly of coiled coil mutants \ of the GCN4 leucine zipper peptide. In our design, the trimeric coiled coil peptide was modified with metal binding ligands at the termini to facilitate higher order assemblies in the presence of metal ions. We report the formation of unprecedented nano- to micron- sized structures obtained from metal-assisted (Zn2+, Co2+, Cu 2+, Ni2+) assemblies of our engineered coiled-coil constructs including hexagonal rods and spheres. Second, we present a unique class of peptides known as cationic amphiphilic polyproline helices (CAPHs), that exhibit antibacterial action against a broad spectrum of pathogenic Gram-positive and Gram-negative bacteria. Additionally, CAPHs also display superior cell penetration with the macrophage cells; the “safe haven” for some of the intracellular resistant bacterial strains. Combining this dual action, CAPHs were able to successfully clear intracellular pathogens (Brucella, Salmonella, Listeria, Shigella) residing within macrophages both in vitro and in vivo (MRSA, Listeria).

Degree

Ph.D.

Advisors

Chmielewski, Purdue University.

Subject Area

Biology|Organic chemistry

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