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4′-Thioadenosine as a Novel Inhibitor of S-Adenosylhomocysteine Hydrolase and an Inducer for the Differentiation of HL-60 Human Leukemia Cells

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Purine and Pyrimidine Metabolism in Man V

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 195B))

Abstract

Analogs of adenosine with modifications in the ribofuranosyl moiety such as (±)aristeromycin (1), 3-deaza-(±)aristeromycin (2-4) and neplanocin A (5) are excellent inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase with competitive Ki and irreversible KI values in the nanomolar ranges. In addition to being inhibitors, some of these modified compounds can also substitute for adenosine as alternative substrates, yielding S-nucleosidinylhomocysteine (NucHcy) analogs (4). Inhibitors of AdoHcy hydrolase will cause elevations in the cellular levels of AdoHcy and/or the production of NucHcy analogs. The main biochemical effect is the inhibition of transmethylation reactions (6-9), normally accompanied by a rise in the S-adenosylmethionine (AdoMet) level. The correlative biological effects are many (4), and chief among them is the induction of differentiation of cell lines. For example, 3-deaza-adenosine enhances the transformation of 3T3-L1 fibroblasts to fat cells upon confluency (10), and 3-deaza-(±)aristeromycin induces the differentiation of HL-60 human promyelocytc leukemia cells to neutrophils (11).

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References

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Authors and Affiliations

  1. Division of Biochemistry, Walter Reed Army Institute of Research, Washington, DC, 20307-5100, USA

    George A. Miura, Richard K. Gordon & Peter K. Chiang

  2. Southern Research Institute, Birmingham, AL, USA

    John A. Montgomery

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  1. George A. Miura
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  2. Richard K. Gordon
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  3. John A. Montgomery
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  4. Peter K. Chiang
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Editor information

Editors and Affiliations

  1. University of California, San Diego La Jolla, California, USA

    W. L. Nyhan

  2. Scripps Clinic and Research Foundation, La Jolla, California, USA

    L. F. Thompson

  3. M. R. C. Clinical Research Center, Harrow, UK

    R. W. E. Watts

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© 1986 Plenum Press, New York

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Miura, G.A., Gordon, R.K., Montgomery, J.A., Chiang, P.K. (1986). 4′-Thioadenosine as a Novel Inhibitor of S-Adenosylhomocysteine Hydrolase and an Inducer for the Differentiation of HL-60 Human Leukemia Cells. In: Nyhan, W.L., Thompson, L.F., Watts, R.W.E. (eds) Purine and Pyrimidine Metabolism in Man V. Advances in Experimental Medicine and Biology, vol 195B. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-1248-2_104

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  • DOI: https://doi.org/10.1007/978-1-4684-1248-2_104

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  • Print ISBN: 978-1-4684-1250-5

  • Online ISBN: 978-1-4684-1248-2

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