Targeting and tuning nucleic acid structures for therapeutic and biotechnology applications

Nucleic acids are essential macromolecules in living cells. Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) have inherent ability to form diverse tertiary structures such as triplex, G-quadruplex, and riboswitch etc., through non-canonical base-pairings. These structures contain additional instructions to control the fundamental cellular processes such as DNA replication, transcription, and translation etc. The nucleic acids structure mediated changes in levels of gene expression are associated with many human diseases including cancer. Thus, nucleic acid structures have emerged as potential therapeutic targets for various diseases. In addition, modular nature of nucleic acids makes it a promising building material for construction of tools such as synthetic switches for solving the problems in medicine and biotechnology.

Our group uses synthetic organic chemistry, molecular biology and biophysical chemistry techniques to get insights into the nucleic acids structure-function relationship in human and bacteria. Next, we apply this obtained knowledge to develop synthetic molecules to target the nucleic acid structures for therapy or to develop synthetic nucleic acids tools to solve problems in biotechnology.

Nucleic acids as tool and target for biomedical and biotechnological applications

The overview of our approaches is as follows:

• India EMBO Lecture Course Grant (2022) as an Organizer from European Molecular Biology Organization.
• Ramalingaswami Re-entry Fellowship (2017).
• Ramanujan Fellowship (2017).
• JSPS Postdoctoral Fellowship (2015).
• The Chemical Society of Japan (CSJ) Oral Presentation Award for the presentation at 97th Annual meeting of the chemical Society of Japan (2017).
• ISNAC Outstanding Oral Presentation Award for the presentation at 43th International Symposium on Nucleic Acids Chemistry, Japan (2016).
• ISNAC Outstanding Poster Presentation Award for the presentation at 40th International Symposium on Nucleic Acids Chemistry, Japan (Nov 2013).
• SPARC Award at a Pharma Company (MNC) Pune, Maharashtra, India (Jan 2008).

• Krushna Shinde
  Junior Research Fellow
  
• Rushikesh Khadake
  Senior Research Fellow
  
• Payal Gupta
  Senior Research Fellow
  
• Divya Ojha
  Project Associate
  
• Manisha Devi
  Junior Research Fellow (Project)
  
• Sachin Yadav
  Project Associate
  

We are looking for willing and enthusiastic students who would like to pursue their research career in this research area. We welcome applications from students for short-term training, six-months dissertation, project, PhD as well as post-doctoral training. Please feel free to contact for any queries (ab.rode@rcb.res.in).

• Kumar R, Singh R, das Chagas Almeida A, da Trindade Granato J, de Oliveira Lemos AS, Kumar K, Patil MT, da Silva AD, Rode AB, Coimbra ES, Salunke DB.Imidazo[1,2-a]pyrimidine as a New Antileishmanial Pharmacophore against Leishmania amazonensis Promastigotes and Amastigotes. ACS Omega. 2023 Oct 20;8(43):40613-40621. doi: 10.1021/acsomega.3c05441. eCollection 2023 Oct 31. PMID: 37929127
• Satange R, Jin P, Hou MH, Rode AB* (2023). Editorial: Non-canonical nucleic acid structures, functions and their applications for understanding human genetic diseases Front. Genet. 14:1188978.
• Gupta P, Khadake RM, Panja S, Shinde K, Rode AB* (2022). Alternative RNA Conformations: Companion or Combatant. Genes 13, 1930
• Gupta P, Ojha D, Nadimetla DN, Bhosale SV, Rode AB* (2022) Tetraphenylethene Derivatives Modulate the RNA Hairpin-G-quadruplex Conformational Equilibria in Proto-Oncogenes. ChemBioChem, e202200131
• Jadhav RW, Wagalgave SM, Kumbhar BV, Khadake RM, Rode AB, Bhosale SV , Bhosale SV*(2022). Aminoglycoside antibiotic kanamycin functionalized tetraphenylethylene molecular probe for highly selective detection of bovine serum albumin protein. Sci Rep., 11526
• Satange R, Rode AB, Hou M* (2022). Revisiting recent unusual drug-DNA complex structures: implications for cancer and neurological disease diagnostics and therapeutics. Bioorg Med Chem, 117094
• Pandey M, Ojha D, Bansal S, Rode AB*, Chawla G* (2021)From bench side to clinic: Potential and challenges of RNA vaccines and therapeutics in infectious diseases. Molecular Aspects of Medicine,101003
• Harale B, Kidwai S, Ojha D, Singh M, Chouhan D, Singh R, Khedkar V, Rode AB* (2021) Synthesis and evaluation of antimycobacterial activity of riboflavin derivatives. Bioorg Med Chem Lett. 48, 128236.
• Ojha D, Rode AB * (2019) Recent Advances in Aptamer Generation for Synthetic Biology Applications. Journal of Japan Society of Nucleic Acids Chemistry (JISNAC), 3:7-11
• Rode AB, Endoh T, Sugimoto N (2018) Crowding Shifts the Riboswitch Aptamer-FMN Recognition Mechanism from Conformational Selection to Induced Fit.Angew Chem Int Ed Engl. 57:6868
• Rode AB, Endoh T, Sugimoto N. (2016) tRNA Shifts the G-quadruplex-Hairpin Conformational Equilibrium in RNA towards the Hairpin Conformer. Angew Chem Int Ed Engl. 55:14319
• Endoh T, Rode AB, Takahashi S, Kataoka Y, Kuwahara M, Sugimoto N. (2016) Real-Time Monitoring of G-Quadruplex Formation during Transcription. Anal Chem 88:1989
• Rode AB, Endoh T, Sugimoto N. (2015) Tuning riboswitch-mediated gene regulation by rational control of aptamer ligand binding properties. Angew Chem Int Ed Engl. 54:909
• Rode AB, Endoh T, Sugimoto N. (2015) Key Tertiary Interactions in FMN Riboswitch Aptamers Required for Ligand Binding. Bull. Chem. Soc. 88: 948
• Rode AB, Endoh T, Tateishi KH, Takahashi S, Sugimoto N. (2013) Real-time monitoring of DNA hybridization kinetics on living cell surfaces. Chem Commun (Camb). 49:8446
• Rode AB, Kim J, Kim SH, Hong IS, (2012) A Highly Selective Chemodosimeter for the Rapid Detection of Hg2+ ions in Aqueous Media. Tetrahedron Lett. 20:2574
• Kim BM, Rode AB, Han EJ, Hong IS, Hong SH. (2012) 5-Phenylselenyl- and 5-methylselenyl-methyl-2'-deoxyuridine induce oxidative stress, DNA damage, and caspase-2-dependent apoptosis in cancer cells. Apoptosis. 17:216
• Rode AB, Kim BM, Park SH, Hong IS, Hong SH. (2011) Potent radiosensitizing agents: 5-methylselenyl- and 5-phenylselenyl-methyl-2'-deoxyuridine. Bioorg Med Chem Lett. 21:1154
• Rode AB, Thajudeen H, Chung KW, Kim YW, Hong IS (2011) Synthesis and Evaluation of Stearic Acid Derivatives as Cetane Number Improvers. Bull. Korean Chem. Soc. 32:1969
• Rode AB, Chung KW, Kim YW, Hong IS. (2010) Synthesis and Cetane-Improving Performance of 1, 2, 4, 5-Tetraoxane and 1, 2, 4, 5, 7, 8-Hexaoxonane Derivatives. Energy & fuels. 24:1639.
• Rode AB, Son SJ, Hong IS. (2010) An Efficient One-pot N-Acylation of Deoxy- and Ribo- cytidine Using Carboxylic Acids Activated in situ with 2-Chloro-4,6-dimethoxy-1,3,5-triazine. Bull. Korean Chem. Soc. 7:2064.
• Shinde SB, Rode AB, Dake SA, Bhosale DS, Pawar RP. (2010) An Expeditious Synthesis of Bioactive 4- Aryl-3, 4-Dihydropyrimidines Using Insitu Generated HCl. International Journal of Industrial Chemistry. 1:51.
• Dake SA, Kulkarni RS, Rode AB, Shinde PS, Ghumbre SK, Magarn RL, Pawar RP (2010) H2O2 /Phosphonium Ionic Liquid: An Efficient and Simple Approach for Benzyl Halides Oxidation. Lett. Org. Chem., 7, 491-494.
• Shinde PS, Shinde SS, Renge AS, Patil GH, Rode AB, Pawar RR (2009) An Efficient Synthesis of Raloxifene in Ionic Liquid: A Green Approach. Lett. Org. Chem. 6:10
• Sarda SR, Puri VA, Rode AB, Dalwale TN, Jadhav WN, Pawar RP (2007) Sulfated Tin Oxides: A Suitable Reagent for Synthesis of 2, 4-diphenyl-4, 6, 7, 8-tetrahydrochromen-5-one. ARKIVOC 16:251



Patents

• S. Asthana, C. Suri, M. Kalia, A. Awasthi, A. Chande, A. Rode, S. Prajapat, S. Sadhu, R.Dalal, V. Bhardwaj, D. Ojha., m-Tor independent autophagy inducing small peptide and therapeutic uses thereof, Indian Patent Application No.: 202011007117, Feb-19-2020
• S. Asthana, C. Suri, M. Kalia, A. Awasthi, A. Chande, A. Rode, S. Prajapat, S. Sadhu, R.Dalal, V. Bhardwaj, D. Ojha., AUTOPHAGY INDUCING PEPTIDES, International Patent Application No.: PCT/IN2021/050799, Feb-24-2022