Studies on nucleotide analogs. I. Synthesis of two 9-alpha-D-mannofuranosyladenine phosphates, and their inhibition of adenylate kinase |
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Authors: | M J Taylor B D Kohn W G Taylor P Kohn |
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Affiliation: | Tissue Culture Section, Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20014 U. S. A.;Department of Biochemistry, Hektoen Institute for Medical Research, Chicago, Illinois 60612 U. S. A.;Tissue Culture Section, Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20014 U. S. A.;Department of Biological Chemistry, University of Illinois at the Medical Center, Chicago, Illinois 60680 U. S. A. |
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Abstract: | 9-α-D-Mannofuranosyladenine (1) was quantitatively phosphorylated at O-5 by phosphoryl chloride in the presence of triethyl phosphate, giving phosphate 2. Treatment of 9-(2,3-O-isopropylidene-α-D-mannofuranosyl)adenine (3) with phosphoryl chloride-trimethyl phosphate, followed by hydrolysis at pH 1.5 to remove the protecting group, yielded mononucleotides 2 and 4 having the phosphate group at C-5′ and C-6′, respectively. These mononucleotides, chromatographically homogeneous in six solvent systems, were further characterized by their patterns of chromatography on Dowex ion-exchange resin, by their mass spectra, and by phosphorus n.m.r. spectroscopy. Both the 5′- and 6′-phosphates are noncompetitive inhibitors of adenylate kinase (for which a sensitive, accurate, and inexpensive, assay-system was developed). Of the two, the 6′-mononucleotide was the more potent inhibitor of adenylate kinase. |
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