The Chemical Biology Unit is located on the campus of the Indian Institute of Science. The work carried out in this unit by the Honorary Faculty Members of JNCASR covers many of the emerging areas of chemical biology.
Recent and current work
Isolation and structure determination of unusual peptides from fungal sources
For example, two new cyclohexadepsipeptides, Isaridin A and Isaridin B, were recently isolated from the fungus Isaria, and characterized by a combination of ESI MS, 500MHz 1H NMR and single crystal X-ray analysis.
Effect of signal peptide on the stability and folding kinetics of Maltose Binding Protein
While the role of the signal sequence in targeting proteins to specific sub-cellular compartments is well characterized, there are fewer studies that characterize its effects on the stability and folding kinetics of the protein. Detailed characterization of the folding kinetics and thermodynamic stabilities of Maltose Binding Protein (MBP) and its precursor form, preMBP have been achieved.
Design of temperature sensitive mutants
Temperature sensitive (Ts) mutants are powerful tools to study gene function in vivo. Ts mutants are typically generated by random mutagenesis followed by laborious screening procedures. Using the E. coli cytotoxin CcdB as a model system, simple procedures for generating Ts mutants at high frequency through site directed mutagenesis have been developed.
Total synthesis of complex bioactive natural products
The idea is to explore these natural products as lead or 'privileged' structures for drug discovery by creating molecular diversity around them. The protocols developed for the total synthesis should lend themselves to ready adaptation to generate small molecule libraries. Recently, the total syntheses of over a dozen molecules of varying degree of complexity were achieved, which exhibit activities ranging from the inhibition of angiogenesis to promotion of apoptosis. Some of these natural products are of great contemporary interest.
Cationic surfactants, novel lipids and nucleic acid analogs
Novel Cationic Surfactants with multiple pyridinium headgroups provide a number of opportunities for application in diverse areas. Such molecules have been synthesized, and their aggregation properties have been investigated using spectroscopic and small-angle neutron scattering studies. A new class of lipids with oxyethylene linkages have been developed and their biophysical properties after membrane formation have been investigated. Cationic Gemini micellar media have been shown to enhance dephosphorylation and deacylation reactions suggesting possible applications for detoxification (nerve gases, pesticides) and enzyme mimics. Using novel strategy distamycin-linked oligonucleotides with chosen sequences have been synthesized. Their duplex formation and related physical characterization has been completed.
Bile acid chemisty
The study of novel analogs of bile acids have led to the design of unusual gelators which have diverse applications. Thus, such bile gels have been used for the design of thermochromic materials, as templates for the design of inorganic nano structures, and also for the anchoring of stabilized metal nanoparticles. A variety of phosphonobile acids are being developed for examining their effect on bile acid metabolism in vivo. Cationic analogs of bile acids are being investigated for cholesterol gallstone dissolution.