SINP Triennial Report - Saha Institute of Nuclear Physics

1 Biophysical Sciences Including
Chemistry
Summary of Research Activities of Divisions
Biophysics
The research activities in Biophysics Division spans both experimental and in silico biology.
The specific areas are as follows: Chemical and Structural Biology, Biomolecular
Spectroscopy, Structural Bioinformatics and Computational Chemistry and Microbiology.
Some of the research activities have collaborative components.
Chemical and Structural Biology:
Small molecules from natural and synthetic sources have long been employed as human
medicine. In the last three years chemical biology of two classes of small molecules with
therapeutic potential has been studied. The first type includes DNA binding molecules
which function at the chromatin level modulating DNA templated phenomena and inhibition
of (core) histone modification enzymes. The studies on the second class of molecules
have been aimed to explore alternate intracellular targets for generic drug(s). In this class
of anticancer antibiotics, mithramycin and chromomycin, have been shown to possess
potential for chelation therapy arising from their bivalent metal ion binding potential. The
antibiotic(s) inhibit the activity of metalloenzymes like alcohol dehydrogenase, alkaline
phsphatase, beta metallolactamase and superoxide dismutase.
In the area of structural biology two problems are being addressed. Sanguinarine and
ellipicin are two putative anticancer agents. They bind to human telomere sequence forming
quadruplex DNA. Telomeric sequences are short stretches of guanine (G)-rich DNA that
occur at the termini of chromosomes and play an important role in chromosome duplication
and are attractive targets for anticancer drugs. The structural modulation induced by these
agents upon the quadruplex structure and the associated energetics are being investigated.
The results show that sanguinarine (SGR) exhibits two distinct interactions with human
telomere d[(TTAGGG)4] (H24) in presence of K+. Up to about 1:2 molar ratio of H24:SGR,
two molecules of SGR bind H24. Above this molar ratio, SGR induces a conformational
transition in H24 from the K+- form to the Na+- form. The demonstration of drug-induced
conformational transition in a G-quadruplex formed by a human telomeric sequence would
provide new insights into interaction of the drugs with quadruplex DNA structure.