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MEYR 546
Phone: 410-455-5784 MEYR 548
Phone: 410-455-3844 MEYR 550
Phone: 410-455-3717 MEYR 552
Phone: 410-455-2562
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Old and New Research Groups Get Together in a Restaurant to Throw a Surprise Birthday Party for Dr. Hosmane in 2004
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This project involves the synthesis and biochemical as well as biophysical studies of novel ring-expanded ("fat") purine nucleosides and nucleotides. With judicious atom insertion at the ring loci and functionalization of the ring periphery, these "fat" nucleotides are potentially capable of Watson‑Crick base‑pair hydrogen bonding with appropriate pyrimidine partners. Because of their unique structures, coupled with novel steric, electronic, and conformational characteristics, these aberrant nucleotides are excellent probes for nucleic acid structure, function, and metabolism. Molecular modeling studies indicate that bulky heterocyclic bases lead to considerable deviations of base-sugar bonds of nucleotides from the natural array. This, in turn, has significant affect upon helical structure, stability, and conformation of polynucleotides that incorporate these aberrant bases. Thus, "fat" nucleotides offer a unique means of exploring steric and conformational constraints of formation of nucleic acid double helices. Furthermore, because of their structural similarity to natural purines, they are also a rich source of substrates or inhibitors of enzymes of nucleic acid metabolism. Our studies are directed toward a) synthesizing various "fat" nucleosides and nucleotides and constructing double helices, each composed of "fat" nucleotides base‑paired with appropriate pyrimidine nucleotide partners, (b) investigations of base-pairing and stacking interactions of homo- and heteropolymer duplexes incorporated with "fat" nucleotides, c) explorations of structural and spatial limitations of formation of double helices, as well as of helical structure, stability and conformations, d) biochemical investigations to determine the potential of "fat" nucleosides and nucleotides to act as substrates or inhibitors of various enzymes of nucleic acid metabolism and of those enzymes requiring energy cofactors, ATP, GTP, CTP or TTP, and (e) investigation of their therapeutic properties for viral and cancer treatments. Base‑mispairing accompanied by considerable deviation of base‑sugar bond deviation from the natural array can potentially result in chain termination of the developing DNA/RNA during transcription or reverse transcription of RNA/DNA genome. Therefore, "fat" nucleosides and nucleotides, have potential applications in viral and cancer chemotherapy.
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