Synthesis and biological activity of a bivalent nucleotide inhibitor of ribonucleotide reductase.
A novel nucleotide inhibitor (ADP-S-HBES-S-dGTP) of mouse ribonucleotide reductase was designed to span the active site and the allosteric specificity site of the enzyme. The inhibitor contains ADP and dGTP moieties which are linked by 1,6-hexane-(bis-ethylenesulfone), and has a Ki value of 12 microM.
Wu
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Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, USA.
Cooperman
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BS
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites; D003848:Deoxyguanine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
D003848:Deoxyguanine Nucleotides; D004791:Enzyme Inhibitors; D000244:Adenosine Diphosphate; C029603:deoxyguanosine triphosphate; D012264:Ribonucleotide Reductases