Synthesis of adenosine-N6-methyl, propylthioether-N-pyridoxamine: an analog of a novel vitamin B6 tumor product.
Studies on the time-course utilization of radiolabeled pyridoxine in rats with hepatomas led to the discovery of a novel vitamin B6 product. It is found in a spectrum of tumor lines but it is absent or occurs minimally in normal tissues. Hepatomas incorporate up to 20-30% of labeled pyridoxine into the novel product. Its structure was tentatively identified as adenosine-N6-methyl, propylthioether-N-pyridoximine-5'-PO4. However, results of tests on the incorporation of labeled precursors into the novel product by 3B3 hybridoma or HL-60 cells support an N6-diethylthioether bridge linking the adenosyl and pyridoxyl moieties. The synthesis of adenosine-N6-methyl, propylthioether-N-pyridoxamine is reported in this paper. The mass spectrum of this analog is similar to that of the tumor product as seen by its fragmentation in further support of the structure of the tumor product. Whether the latter may be part of tumor RNA is questionable. RNA was isolated for 3B3 or HL-60 cells after incubation with tritiated or 14C-pyridoxine using SDS-phenol repeated extractions in the presence of RNase inhibitors. Centrifugation of cRNA on 5-20% linear sucrose density gradients showed practically all the label at the top of the gradient. RNase treatment resulted in a labeled product which coeluted with the tumor product on reverse phase paired-ion HPLC and chromatographed as dinucleotide on paper. These results suggest that the novel tumor product may occur as a short oligonucleotide.
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Department of Biochemistry, West Virginia University, North Morgantown 26506.
Bishop
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D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification; D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006825:Hybridomas; D007202:Indicators and Reagents; D015473:Leukemia, Promyelocytic, Acute; D013058:Mass Spectrometry; D051379:Mice; D011733:Pyridoxamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification; D011736:Pyridoxine / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000302:isolation & purification; D014316:Tritium
D007202:Indicators and Reagents; D012334:RNA, Neoplasm; D014316:Tritium; C072610:adenosine-N(6)-methyl-propylthioether-N-pyridoxamine; D011733:Pyridoxamine; D000241:Adenosine; D011736:Pyridoxine