Dr. Chhuttan Lal Meena

Research Interest:

Medicinal chemistry and molecular pharmacology, target-based drug discovery, using peptide-library, Synthesis of peptides and peptidomimetic and bioactive organic molecules bycombinatorial synthesis and manual synthesis, and high throughput screening using affinity selection mass spectroscopy (AS-MS).The discovery of nucleic acid-based drugs,their alternative mode of action, the synthesis of PNAs based artificial oligonucleotides as antimicrobial agents, led to the elimination of harmful infections.

Summary of Research:

Aim-1:The core of our research is target-based drug design, organic synthesis, medicinal chemistry, and drug discovery, but we also develop assays, screen samples through high-throughput screening, analyze ligand-receptors/enzymes biochemical and biophysical assay, X-ray crystallography, characterization of molecules structures by 1H/13CNMR, DEPT Optical rotation,UV, LC-MS, HRMS,MALDI and in-silico studies using homology modeling, molecular docking, MD simulation, and structure-based drug discovery. The goal of our research is to develop peptide libraries through combinatorial methods, chemical modifications, head to tail cyclization, partial cyclization, peptidomimetic, small organic molecules, microwave synthesis and initially, identify high affinity binders (peptide based, organic based for serine proteases, using affinity selection mass spectroscopy (AS-MS), attached with nano shotgun mass spectroscopy(nLC/MS) and rational chemical modifications.

Aim-2:Every year, millions of people are affected by uropathogens like Gram-positive and Gram-negative bacteria and fungi. It is estimated that approximately 50% of women in India or world suffer from urinary tract infections during their lifetime and that this causes very high healthcare costs annually. This project will develop leads for preclinical candidate therapeutics to treat and prevent the growing tide of antibiotic-resistant bacterial pathogens that are causing common infections to become increasingly difficult to treat. We will use affinity selection mass spectroscopy (AS-MS) attached with nano shotgun mass spectroscopy (nLC/MS) for finding potent lead molecules. This approach will result in developing compounds like peptide libraries, heterocyclic molecules and carbohydrate-based molecules which are active against both antibiotic-resistant and antibiotic-sensitive pathogens.

Aim-3:The development of artificial oligonucleotides-based antimicrobial agents with different mode of action then existing antibiotics leads to complete elimination of harmful microbial infection. Recently, artificial nucleobase containing PNAs and PNA mimics are developed as sequence specific inhibitors of ds DNA or Pre-mRNA translation and transcription (antisense and antigen) oligonucleotides for manipulation of gene function within the cells to treat large number of diseases. Recently, novel hybridnucleobases, and PNA intermediates has been discovered. Hypothesizing that these hybrid nucleobases could be used to manipulate gene functions. This project will synthesize artificial short oligonucleotides containing hybrid nucleobase to develop PNA based antibiotics to target essential bacterial gene expression.

Awards:
2011: Fulbright-Nehru Doctoral Fellowship award USIEF, NIH/NIDDK, MD, USA
2007: Rajiv Gandhi National Fellowship Awards, University Grant Commission New Delhi, India
2006: Engineering and Technology Fellowship awards, University Grant Commission New Delhi, India

Patents:
1. C.L.Meena; D. Singh, G.J. Gangadhar, Triazine-Based Self-assembling System,WO/2022/162689, Indian, patent 2022.
2. C. L. Meena; T. Hingamire, D. Shanmugam; G.J. Sanjayan. Discovery of peptide histidinal conjugates as potent Anti-malarial agents under Indian, provisional.11/02/2022 INV-2022-010, 2023