The objectives of the research center on the synthesis and testing of dimensional probes, purine and pyrimidine ring analogues with known dimensional alterations, of enzyme-coenzyme binding sites. For example, one purpose if to assess the size of the space available to the adenine moiety in the case of ATP by means of such dimensional probes or """"""""stretched-out"""""""" analogues. The importance of ATP is illustrated by the calculation that a person uses and resynthesizes ATP daily to the extent of an equivalent of body weight. The fluorescence of the synthetic analogues of ATP enabales them to be used, by fluorescence displacement titration, for the characterization of adenine nucleotide binding sites of important enzymes. A """"""""stretched-up"""""""" version of uracil, consisting of two fused, coplanar five-membered rings, will be used to investigate its potential interference with pyrimidine metabolic processes through similar or competitive enzyme binding, which in turn may lead to the development of cytotoxic, antibacterial, and antiviral compounds in this """"""""stretched-up"""""""" series. Investigation of the chemical modification of the natural nucleosides and nucleotides is undertaken with the combined aims of (1) characterizing both the substrate and the receptor site by means of the incorporated fluorescence properties and (2) determining the effect of switching hydrogen-bonding characteristics in monomer or polymer compositions of the nucleosides and nucleotides.
| Mudry, Ryan E; Perry, Cynthia N; Richards, Meredith et al. (2003) The interaction of tropomodulin with tropomyosin stabilizes thin filaments in cardiac myocytes. J Cell Biol 162:1057-68 |
| Hill Jr, A R; Kumar, S; Patil, V D et al. (1991) Which 3-ribofuranosyl-substituted purine 5'-phosphates undergo template-directed oligomerization? J Mol Evol 32:447-53 |
| Kumar, S; Patil, V D; Wilson, S R et al. (1989) Structure of 3-isoinosine. Acta Crystallogr C 45 ( Pt 9):1394-7 |
| Hill Jr, A R; Kumar, S; Leonard, N J et al. (1988) Template-directed oligomerization of 3-isoadenosine 5'-phosphate. J Mol Evol 27:91-5 |
| Kumar, S; Wilson, S R; Leonard, N J (1988) Structure of 3-isoadenosine. Acta Crystallogr C 44 ( Pt 3):508-10 |
