Date of Award

12-2014

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Environmental Science

First Advisor

Dr. Alaa Eldin Salem

Second Advisor

Dr. Muna Bufaroosha

Third Advisor

Dr. Ahmed AIMehdi

Abstract

Nucleic acids control the machinery of living cells through coding different biochemical functions. Metal ions play a critical role in including and stabilizing different DNA structural conformations through interacting with various sites on nucleic acids. Interactions are controlled by the relative affinity of metal ions towards the negatively charged phosphate backbone and donor nitrogen or oxygen on nucleotide bases. Several studies have investigated the interactions of metal ions with duplex and higher orders DNA conformations. These interactions vary greatly, from monovalent alkali ion that are primarily delocalized in a diffuse cloud around duplex DNA to transition metals that are directly coordinated to the nucleotide bases.

The main objective in our work was to study the interaction of trivalent metal ions with human telomere random coil single stranded and GQ DNAs as well as with double stranded calf thymus DNA. Understanding their mode of interactions, ability to induce secondary order DNA conformations and stabilization of resultant structure are vital goals of this study.

In this work, we studied the interaction of 9 metal ions including lanthanide ions Ce3+, Sm3+, Dy3+, Gd3+, Ho3+, Tb3+ and heavy metal ions Rh3+, Os3+, and AU3+ with different DNAs. Investigation were done using UV-Vis, fluorescence and circular dichroism techniques. The study was carried out in aqueous solutions using Tris buffer, pH 7.4.

Results of UV-Vis, Circular dichroism and fluorescence measurements indicated that the trivalent metal ions interact with human telomere single strand random coil and G-quadruplex DNA through guanine bases, at low concentrations. Trivalent ions induced transformations of random coil DNA to anti-parallel G-quadruplex. Results also indicated that ct-DNA interacted with lanthanide metal ions through an intercalation binding modes and with a mixed binding mode including intercalations and electrostatic binding for Rh3+, Os3+ and Au3+ ions.

The results gave insights on how trivalent metal ions affect the conformations of different DNA strands and subsequently contribute in controlling cell machinery. The results are highly importance for future designing of anticancer and anti-neurodegenerative drugs.

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