Title: Cyclic Peptide Containing Disubstituted β- and γ-amino Acid as Antimicrobial Agents
Funder: The Academy of Medical Sciences

Abstract: At this time when we are going through an unprecedented global pandemic, it is an unarguable fact that new and advanced drugs are of paramount importance. A pressing issue is the development of new medicines that treat microbial infections to prevent the growing health threat posed by resistant pathogenic microorganisms. Being able to control drug-resistant strains of gram-negative bacteria, without prolonging the course of treatment is even more challenging. Amongst the naturally occurring antimicrobial peptides, cyclic peptides have exhibited traits of potential antibiotics due to their diverse biological properties and metabolic stability compared to linear peptides. Their peculiar heterocyclic system found in several natural products constitutes a rich source of new biologically active compounds. Naturally occurring cyclopeptides isolated from fungi, plants and bacteria have been reported to target and disrupt the functions of microbial cell membranes. Major problems associated with such natural peptides are their low bioavailability, low metabolic, proteolytic stability, complex structures and high cost of goods. To overcome the inherent limitation, these peptides can be modified using the peptidomimetic approach by introducing β- and/or γ-amino acid to develop short and potent peptide therapeutic agents against microbial infections. The present proposal aims to develop novel cyclic peptides incorporating non-proteinogenic β- and γ-amino acids with potent antimicrobial properties.

Lay abstract: Effective drug therapy ranks high among the scientific advances that have changed our lives over the past century. Cures of infectious diseases and treatments of drug-resistant microbial infections have dramatically rehabilitated lives. Yet, we are still at the beginning of developing truly effective therapies to prevent antibiotic resistance diseases. My research project attempts to investigate the possibilities of drug discovery to prevent the growing health threat posed by microorganisms. As it is said, When One Door Closes Another Opens, past research hints that hybrid cyclic peptides containing synthetic amino acids have better stability and have exhibited traits of potential antibiotics due to their diverse biological properties, and less resistance towards the microbial strains than naturally occurring peptides. My research is relevant as well as challenging because it is impossible to regulate the eating pattern of our diverse society but what we can do is look for a cure in naturally occurring substances. Yet again, a pandemic has revealed cracks in our medical preparedness, so it becomes even more crucial to equip ourselves with future proof drugs to ensure a healthy world. This project focused on the development of peptide-based antimicrobial drugs against microbial resistance and to improve proteolytic stability, biocompatibility and economic antimicrobial peptide drugs. Findings from this project can be fostered within India in the development of pharmaceutical industries. The improvement will be reflected in a positive outcome for the peptide drug to overcome microbial resistance and lead to improved social welfare and economic development.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: INFECTION