Presenter: Nauman Nazeer

Title: “Design, Synthesis, and Secondary Structure Stabilization of Self-Assembling Antimicrobial Peptides”

Synthetic antimicrobial peptides (AMPs) possess broad-spectrum antimicrobial activity, immunomodulatory properties, and the ability to self-assemble into various nanostructures. However, many synthetic AMPs display secondary structure instability which leads to host toxicity, low selectivity, and aggregation that limits their application in clinical settings. This thesis investigates the use of rational approaches to design synthetic self-assembling AMPs that can address these issues. A library of peptides was designed based on chicken Angiogenin-4 (chAng4) protein as a template. From this library, a macrocyclic mini-peptide derived from chAng4 (mCA4-5) was found to be effective against a variety of pathogenic Gram-positive and Gram-negative strains. To obtain more stable secondary structures, analogues of mCA4-5 with varying hydrophobicity, net charge, chirality, and modes of cyclization were synthesized. Lactam-cyclized analogues of mCA4-5 were found to have more stable secondary structures with improved antibacterial activity, bacterial flocculation, proteolytic stability, and proinflammatory activity. Therefore, the techniques described in these studies could be useful for the rational design of novel AMP-based nanomaterials with constrained and stabilized secondary structures for applications such as drug delivery, antimicrobial coatings, wound healing, and immunotherapy.

Date/Time/Location: Friday, June 28, 2024, 1:30 pm in AVC 287N

Everyone is welcome.