Research Groups

Mammalian Biology: Malaria

Research Interests and Description

Staff Research Scientist: Dinkar Sahal

Group Leader: Virander Chauhan

Group Members

Research Interests

Novel antibiotics by de novo design, novel antimalarial drugs from nature.

Description of Research

Designing antibacterial Peptides
The Group's motivation is designing potent, safe and economic antimicrobial peptides. We have expanded the syntax of antibiotics by demonstrating (a) the potentiating effect of a Lysine branched dimerization motif for a large number of antimicrobial peptides, (b) the value addition in potency with aromaticity, helicity and protease stability, and (c) the potential of didehydrophenylalanine in designing novel versatile antibiotics. A battery of properties including LPS binding, membrane permeabilization, DNA binding, protein coagulation, protease stability, peptide penetration kinetics, MIC, MBC, Cell kill kinetics, hemolysis and cytotoxicity have facilitated our ability to evolve the parameters that influence specificity and potency of antibiotic action.

Novel antimalarials from nature
It is ironic that with all the advances made in Biology and public health, Malaria continues to torment mankind even today in the 21^st century. Since the malaria parasite of today has learnt to resist the killing action of most antimalarial drugs, there is acute need to identify novel drugs against malaria. Most drugs in the clinic have their origins in Nature. The probable reason for this may be that owing to their long evolutionary history, nature's molecules may have learnt to rub shoulders with diverse cellular milieus. We have been making rapid progress in fishing out potent and safe antimalarials from marine organisms. In collaboration with Dr.Padma kumar, a distinguished marine biologist of the University of Trivandrum, we have examined over 200 marine extracts for their potential antimalarial activities. Our High throughput microtiter plate based screens include (a) heme detoxification based Heme-PfHRPII colorimetric screen and (b) Blood stage P.falciparum growth in culture based on SYBR Green I fluorescence. We have screened more than 200 extracts and have discovered several molecules which show potent action (IC₅₀ < 1 mg/ml) against the malaria parasite. We are engaged in purifying these leads to homogeneity for determination of their chemical structures and chemical synthesis of promising molecules toward drug trials.

Recent Publications

Dewan, P.C., Anantharaman, A., Chauhan, V.S., Sahal, D. 2009. Antimicrobial Action of Prototypic Amphipathic Cationic Decapeptides and Their Branched Dimers. Biochemistry 48, 5642-5657

Pooja C.Dewan, Aparna Anantharaman, Virander S.Chauhan and Dinkar Sahal Antimicrobial Action of Prototypic Amphipathic Cationic Decapeptides and Their Branched Dimers . Biochemistry 2009, 48, 5642-5657

Jagdish Rai, Raghothama, S., Sahal, D. 2007. De novo design of DF containing peptides. Chemical Biology and Drug Design. Chem Biol Drug Des. 69, 119-123

Jagdish Rai, Raghothama, S., Sahal, D. 2007. Tyrosine-heme ligation in Heme- peptide complex: design based on conserved motif of catalase. J Pept Sci. 13, 406-412

Pal-Bhaumick, I., Pati Pandey, R., Jarori, G.K., Kar, S., Sahal, D. 2007. Structural and functional studies on Ribonuclease S, Retro S and Retro Inverso S peptides. Biochem Biophys Res Commun. 364, 608-613

Chetal, P., Chauhan, V.S., Sahal, D. 2005. A Meccano set approach of joining trpzip a water soluble β-hairpin peptide with a didehydrophenylalanine containing hydrophobic helical peptide. J. Peptide Res. 65, 475-484