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Biomacromolecule-ligand interactions

By Jemma C. Peberdy

Abstract

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

Topics: QD, QP
OAI identifier: oai:wrap.warwick.ac.uk:4069

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