Biomacromolecule-ligand interactions
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Abstract
The interactions and binding of various ligands to biomacromoleculcs e.g. DNA and
proteins finds widespread application in the design and development of novel
pharmaceuticals. DNA has been identified as the target molecule for a number of drugs
and carcinogens and the supramolecular synthetic approach has led to the discovery of a
range of bimetallo iron cylinders that bind to DNA inducing remarkable structural
effects. The cylinders arc chiral and the enantiomers were separated on cellulose packed
in paper or in a column. The optimum mobile phase for efficient separation was found
to be 90% acctonitrilc: 10% 0.02 M NaCl. The (M)-enantiomers of the parent cylinder
have been found to bind to DNA in the major groove. I Hydrophobic methyl groups were
added at various positions on the ligand backbone. UV/visible absorbance, circular and
linear dichroism were used to investigate any interactions of the metal complex with
DNA with the aim of investigating any sequence preference or selectivity upon binding.
Competitive binding studies and molecular dynamics simulations were used to probe
the binding geometries of the enantiomers of the parent cylinder and two methylated
cylinders to DNA as the exact site of interaction of the (P)-enantiomers of the parent
cylinder was unclear. It was concluded that the methylated bimetallo iron cylinders bind
to DNA and provide major groove recognition and may show some sequence
preference.
Circular dichroism was used to structurally characterise a range of buanosine-rich
oligonucleotides (GRO's) and to investigate their interactions with a nucleolar protein
- nucicolin. Biological/anti-proliferative activity has been related to the ability of the
oligonucleotide to bind to this protein. It was found that nucleolin does bind to a
biologically active GRO in the presence of K+ and induces a structural change in it