My long-term objective is to identify the roles of posttranscriptional modifications in the coordination of selective metal ions to several modified nucleosides and oligonucleotides. Oligonucleotides containing selected modified nucleosides will coordinate to a certain metal strongly and this may enhance their catalytic activity, i.e., their ability to function as ribozymes or coenzymes. Ultraviolet (UV) spectrophotometry, fluorescence, and NMR will be used to study the coordination of Mg+2, Mn+2, Cd+2, Pb+2, and Hg+2 to uridine (mostly as control) and to several of its naturally-occuring modifications. The roles of water of hydration, and the phosphate group of oligonucleotides in metal coordination will be examined. The generated data will guide the synthesis of short oligonucleotides which, by the inclusion of selected modified nucleosides, will coordinate tightly to certain metal ions. Metal coordination to oligonucleotides will also assist in explaining some of the heavy metals toxic biological effects as they bind to RNAs. Specifically my aims are: 1) Mg+2, Mn+2, Cd+2, Pb+2, and Hg+2 binding constants and the identification of these metals' coordination sites to uridine (mostly as a control) and several modified uridines will be determined. 2) By carrying out the metal coordination study in dimethylsulphoxide (DMSO) and comparing it with that in water, this study will explain the role of water of hydration. Steric and pH effects will be investigated. 3) Role of the phosphate group, among other aspects, in metal coordination to short oligonuceotides that contain selected modified nucleosides will be surveyed. 4) This broad metal coordination study may then assist in designing oligonucleotides whose tight metal binding may enhance their catalytic activity, i.e., their ability to function as ribozymes or coenzymes. In light of their toxic effects, this broad study will also correlate the coordination of heavy metals to a specific RNA (tRNA, snoRNA) molecule to the presence of certain modified nucleosides. The different possible biological pathways resulting from such binding will be examined.
| Wang, Yongmei; Rader, A J; Bahar, Ivet et al. (2004) Global ribosome motions revealed with elastic network model. J Struct Biol 147:302-14 |
| Adebodun, F; Scott, C E; Cunningham, C et al. (2000) Elevated levels of Ca(II) modulate the activity and inhibition of serine proteases: implication in the mechanism of apoptosis. Cell Biochem Funct 18:59-66 |
| Scott, C E; Adebodun, F (1999) 13C-NMR investigation of protein synthesis during apoptosis in human leukemic cell lines. J Cell Physiol 181:147-52 |
| Adebodun, F (1999) Phospholipid metabolism and resistance to glucocorticoid-induced apoptosis in a human leukemic cell line: a 31P-NMR study using a phosphonium analog of choline. Cancer Lett 140:189-94 |
| Jordan, L M; Russo-Marie, F (1992) Purification and partial characterization of phospholipase A2 isoforms from human placenta. J Chromatogr 597:299-308 |
