Relationship Between the Structure of Sangivamycin-Derived Nucleosides and Their Effect on Leukemic Cell Growth and on Protein Kinase A and C Activity
- 1 March 1994
- journal article
- research article
- Published by Taylor & Francis in Nucleosides and Nucleotides
- Vol. 13 (1-3) , 429-435
- https://doi.org/10.1080/15257779408013252
Abstract
The nucleoside antibiotic sangivamycin (4-amino-7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide, (1) is an effective inhibitor of protein kinase A (PKA) and protein kinase C (PKC) but, upon its phosphorylation in intact cells, it gains the ability to affect other targets as well. To retain its selectivity for the protein kinases, a series of nonphosphorylatable sangivamycin derivatives was prepared by replacing the 5′-hydroxyl group with other functions including N3, F, SO2NH2, NO2, and NH2, These derivatives were more potent inhibitors of PKA and PKC than were the phosphorylatable compounds, although the latter were more potent inhibitors of leukemic cell growth.Keywords
This publication has 10 references indexed in Scilit:
- A Practical Synthesis of The Antibiotic ToyocamycinNucleosides and Nucleotides, 1993
- Synthesis of 5′-Substituted Derivatives of the Pyrrolo[2,3-d]-Pyrimidine Nucleoside Sangivamycin and Their Effect on Protein Kinase A and C ActivityNucleosides and Nucleotides, 1993
- Protein kinase C in transmembrane signallingFEBS Letters, 1990
- Site-Selective Cyclic AMP Analogs as New Biological Tools in Growth Control, Differentiation, and Proto-oncogene RegulationCancer Investigation, 1989
- Nucleoside syntheses, XXII1)Nucleoside synthesis with trimethylsilyl triflate and perchlorate as catalystsEuropean Journal of Inorganic Chemistry, 1981
- Synthesis and biological activity of 4'-thio analogs of the antibiotic toyocamycinJournal of Medicinal Chemistry, 1972
- Pyrrolopyrimidine nucleosides. V. Relative chemical reactivity of the 5-cyano group of the nucleoside antibiotic toyocamycin and desaminotoyocamycin. Synthesis of analogs of sangivamycinThe Journal of Organic Chemistry, 1970
- Pyrrolopyrimidine nucleosides. III. Total synthesis of toyocamycin, sangivamycin, tubercidin, and related derivativesJournal of the American Chemical Society, 1969
- Structure of sangivamycinJournal of Medicinal Chemistry, 1968
- Synthese von IsothiocyanatenEuropean Journal of Organic Chemistry, 1962