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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM034125-01
Application #
3284644
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1984-12-01
Project End
1988-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
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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