Oral Presentation 10th Australian Peptide Conference 2013

Functional designed peptides: Antimicrobials and enzymes (#73)

Surajit Bhattacharyya 1
  1. Nanyang Technological University, Singapore

De novo designed active peptides are of significant interest. Such peptides can be potentially utilized as novel therapeutics and catalysts. Further, designing folded peptides allow us to examine fundamental problems of protein structure and folding. We are developing two groups of peptides: broad-spectrum antimicrobial/anti-endotoxic and membrane protein mimics. Antimicrobial peptides (AMPs) have high potential as novel antibiotics active against multiple drug resistance (MDR) pathogens. Among drug-resistant bacteria, Gram-negative ones are of significant threats due to the lack of potent antibiotic in drug discovery pipelines. The outer membrane or lipopolysaccharide (LPS) of Gram negative bacteria acts as a permeability barrier against antimicrobial agents. LPS or endotoxin is also well known for sepsis mediate mortality. In our studies, we have developed peptides those act through LPS-outer-membrane. These peptides adopt boomerang like beta-structures in complex with LPS lipids. Further, we have observed that hybrid peptides obtained from boomerang motif conjugated with inactive (against Gram negative bacteria) AMPs are highly potent against drug-resistant Gram negative bacteria. In another project, we have designed beta-hairpin peptides (IV8) with heme binding and peroxidase activities in lipid membrane. NMR structure of IV8 has been determined in detergent micelles. This research has implications in membrane protein design with novel functions.

  1. Beta-Hairpin peptides: heme binding, catalysis and structure in detergent micelles.. Angewandte Chemie (published On-line).
  2. Lipopolysaccharide neutralizing peptide-porphyrin conjugates for effective photo-inactivation and intracellular imaging of gram-negative bacteria strains. Fang Liu, Annie Soh Yan Ni, Yingjie Lim, Harini Mohanram, Surajit Bhattacharjya and Bengang Xing. Bioconjugate Chemistry (2012), 23, 1639-1647.
  3. Designed beta-boomerang antiendotoxic and antimicrobial peptides: structures and activities in lipopolysaccharide. Anirban Bhunia, Harini Mohanram, Prerna N. Domadia, Jaume Torres, and Surajit Bhattacharjya. Journal of Biological Chemistry (2009), 284, 21991-22004.
  4. Designed beta-boomerang antiendotoxic and antimicrobial peptides: structures and activities in lipopolysaccharide. Anirban Bhunia, Harini Mohanram, Prerna N. Domadia, Jaume Torres, and Surajit Bhattacharjya. Journal of Biological Chemistry (2009), 284, 21991-22004.