Dr. Chhuttan Lal Meena
Research Interest:
Summary of Research:Our research integrates medicinal chemistry and target-based drug design to develop novel therapeutics, with a particular focus on peptides and small organic molecules. We employ a multidisciplinary approach that combines synthetic chemistry, in silico modelling, and biological evaluation.
Key Techniques: Peptide and Organic Synthesis: Solid-phase and solution-phase synthesis of linear and cyclic peptides, including head-to-tail cyclization, partial cyclization, and chemical modifications to generate diverse peptide libraries. Computational Drug Design: Molecular docking and molecular dynamics (MD) simulations to predict and refine target-ligand interactions. Comprehensive analysis using 1H/13C NMR, DEPT, optical rotation, UV spectroscopy, LC-MS, and HRMS for structural confirmation and purity assessment. Biological and Biophysical Assays: Ligand-receptor and enzyme-based assays, including biochemical and biophysical evaluations of activity. X-ray crystallography (in collaboration) to elucidate target-ligand structures at atomic resolution.
Research Goal:
This project is focused on the design and optimization of peptide-based libraries and small-molecule scaffolds to modulate clinically relevant biological targets. The overarching aim is to develop novel antimicrobial agents, vaccine adjuvants, cancer therapeutics, and gene-targeting platforms. A major thrust of this research involves the use of artificial oligonucleotide-based systems particularly peptide nucleic acids (PNAs) as antimicrobial agents with mechanisms distinct from those of existing antibiotics, offering the potential for complete eradication of harmful microbial infections.
Our lab includes the development of artificial nucleobase-containing PNAs and PNA mimics that function as sequence-specific inhibitors of double-stranded DNA or pre-mRNA, acting through antisense or antigene mechanisms. These synthetic oligonucleotides enable precise manipulation of gene function within cells, opening new avenues for the treatment of a wide range of diseases. Notably, we have discovered novel hybrid nucleobases, hypothesizing that these structural innovations can be harnessed to selectively interfere with essential bacterial gene expression. The current project will synthesize short artificial oligonucleotides incorporating these hybrid nucleobases, with the goal of developing next-generation PNA-based antibiotics targeting bacterial transcription and translation pathways critical for survival.
Aim-1: 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. 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 hybrid nucleobases have been discovered these hybrid nucleobases could be used to manipulate gene functions. This project will synthesize antisense oligonucleotides (ASO) containing hybrid nucleobase to develop PNA based antibiotics to target essential bacterial gene expression.
Group Members:
Mr. Vineet Singh (Lab assistant)
Ms. Udita Ghosh (PhD Scholar)
Ms. Priyanka Subba (PhD Scholar)
Ms. Nitika Arora (PhD Scholar)
Mr. Vineet Singh (Lab assistant)
Ms. Udita Ghosh (PhD Scholar)
Ms. Priyanka Subba (PhD Scholar)
Ms. Nitika Arora (PhD Scholar)
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
Funding:
NII Core, Science and Engineering Research Board (SERB)
Patents:
1. C. L. Meena; D. Singh, G.J. Gangadhar, Triazine-Based Self-assembling System, WO/2022/162689, USA, US 2024/0076274 A1 07-03-2024.
2. C. L. Meena; T. Hingamire, D. Shanmugam; G.J. Sanjayan. Discovery of peptide histidinal conjugates as potent anti-malarial agents under PCT/IN2024/050002, PCT/IN2024/050002, Your ref: 0163NF2022_WO (Lab: NCL), Our Ref No: RCY# P_WO100682.
Publications:
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S. Agarwal, H. H. Chandpa, S. Naskar, C. L. Meena, A. K. Panda, J. Meena Dominant B cell-T cell epitopes instigated robust immune response in-silico against Scrub Typhus. doi.org/ 10.1016/ j. vaccine. 2024. 04.082 Vaccine, Available online 7 May 2024
- S. Agarwal, H. H. Chandpa, S. Naskar, C. L. Meena, A. K. Panda, J. Meena Dominant B cell-T cell epitopes instigated robust immune response in-silico against Scrub Typhus. doi.org/ 10.1016/ j. vaccine. 2024. 04.082 Vaccine, Available online 7 May 2024
- H. H. Chandpa, A. K. Panda, C. L. Meena, J. Meena, Vaccine, xx (xxxx) xx. Beyond the polysaccharide and glycoconjugate vaccines for Streptococcus pneumoniae: Does protein/peptide nanovaccines hold promises? Accepted 8 Nov 2023, https://doi.org/10.1016/j.vaccine.2023.11.020
- Singh, D.; Meena C.L.; Lakshmi D.; Krishna G.R.; Sanjayan, G.J. Carbamate-Protected (BOC and O-NB) 2-Aminopyrimidinedione-Based Janus G-C Nucleobase Motifs as Building Blocks for Supramolecular Assembly and Smart Polymers. J. Org. Chem. Oct. 18, 2023, XXXX, XXX, XXX-XXX; Publication https://doi.org/10.1021/acs.joc.3c01318.
- Meena C. L; Hingamire T.; Gupta, T.; Deshmukh, B.; Karmodiya, K.; Joshi, R.Histidinal-Based Potent Antimalarial Agents. ChemMedChem. 2023,e202200709
- Mondal, S.; Lessard, J. J.; Meena, C. L.; Sanjayan, G. J.; Sumerlin B.S. Janus Crosslinks in Supramolecular Networks, J. Am. Chem. Soc. 2022, 144, 2, 845–853.
- Meena C.L.; Singh, D.; Bhavya, K.; Prasad, M.; Malini, G.; Tothadi. S.; Sanjayan, G.J. Triazine-based Janus G-C Nucleobase as a Building Block for Self-Assembly, Peptide Nucleic Acids and Smart Polymers. J. Org. Chem. 2021, 86, 4, 3186–3195.
- Meena C. L.; Shaliwal R. P., Kumar, V., Kumar, A. Tiwari, A.K.; Asthana, S.; Ramandeep Singh, Mahajan D,Synthesis and evaluation of thiophene based small molecules as potent inhibitors of Mycobacterium tuberculosis. Eur. J. Med. Chem. 2020, 208, 112772.
- Meena C. L.; Singh. D.; Weinmüller, M.; Florian, R.; Zahler, H.; Sanjayan, G.J., Novel Cilengitide-based cyclic RGD peptides as αvβ3 integrin inhibitors.Bioorg. Med. Chem. Lett, 2020,30, 127039.
- Meena, C. L.; Thakur, A; Rajpoot, S. Nandekar P.; Sangamwar, A.T; Sharma, S.S.; Kumar; Jain, R; Synthesis and biology of ring-modified L-Histidine containing thyrotropin-releasing hormone (TRH) analogues.Eur. J. Med. Chem. 2016, 111, 72-83.
- Meena, C. L.; Ingole, S. Thakur, A; Rajpoot, S. Nandekar P.; Sangamwar, A.T; Sharma.; Sharma S. S.; Jain,Discovery of a low affinity thyrotropin-releasing hormone (TRH)-like peptide that exhibits potent inhibition of scopolamine-induced memory impairment in mice. RRSC Adv., 2015, 5, 56872.
- Meena, C. L.; Ingole, S. Thakur, A; Rajpoot, S. Nandekar P.; Sangamwar, A.T; Sharma, S.S.; Kumar N.; Jain,R, Synthesis of CNS active thyrotropin-releasing hormone (TRH)-like peptides: Biological evaluation and effect on cognitive impairment induced by cerebral ischemia in mice. Bioorg. Med. Chem. 2015, 23, 5641–5653.
- Monga V.; Meena, C. L.; Kaur, N.; Jain, R.; Chemistry and Biology of Thyrotropin-releasing hormone (TRH)and its analogues. Curr. Med. Chem. 2008, 15, 2718-2733.
- Monga, V.; Meena, C. L.; Rajput, S.; Pawar, C.; Sharma, S. S.; Lu, X.; Gershengorn, M. C.; Jain, R. Synthesis, Receptor Binding, and CNS Pharmacological Studies of New Thyrotropin-Releasing Hormone (TRH) Analogues Chem Med Chem. 2011, 6, 531-543.
- Kidwai, S.; Bouzeyen, R.; Chakraborti, S.; Khare, N.; Sumana Das, S.; Gosain, T. P.; Behura, A.; Meena, C. L.;Dhiman, R.; Essafi, M.; Bajaj, A.; Saini, D.K.; Srinivasan, N.; Mahajan, D.; Singh R.; NU-6027 Inhibits Growth of Mycobacterium tuberculosis by Targeting Protein Kinase D and Protein Kinase G. Antimicrob. AgentsChemother. 2019, AAC.00996-19
