Adenine-arginine mimetics as bisubstrate analog inhibitors of cAMP-dependent protein kinase

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 7, 1996, Pages 899-902

  Ho, Mengfei ^a   Wilson, Brenda A ^a   Katampe, Ibrahim ^a  

^a WRIGHT STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENINE DERIVATIVE; ADENOSINE; CYCLIC AMP DEPENDENT PROTEIN KINASE; GUANIDINE DERIVATIVE; PROTEIN KINASE INHIBITOR;

ARTICLE; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; NUCLEAR MAGNETIC RESONANCE;

EID: 0029915811     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00140-0     Document Type: Article

References (16)

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4. Kemp, B. E.; Parker, M. W.; Hu, S.; Tiganis, T.; House, C. TIBS, 1994, 19, 440.
5. 1H NMR.
6. The conversion, monitored by HPLC (Vydac C-18 column), was found to be 80% after 24 h, with no significant improvement after longer reaction time or addition of more reagent.
7. 13C NMR: 1a (42.4, 45.1, 119.7, 146.2, 146.5, 150.6, 151.6, 158.8 ppm); 1b (41.3, 44.2, 68.5, 69.0, 118.1, 144.9, 145.8, 148.9, 150.8, 157.4 ppm); 1c (41.4, 44.3, 68.4, 69.0, 69.8, 117.7, 144.5, 145.2, 148.8, 149.9, 157.6 ppm). For 1c, the chemical shift at 69.8 ppm was assigned as two overlapping signals.
8. 4 (3x), then methanol, and allowed to dry. The amount of radioactivity was quantified on a Molecular Dynamics Phospholmager.
9. Kemp, B. E.; Graves, D. J.; Benjamini, E.; Krebs, E. G. J. Biol. Chem. 1977, 252, 4888.
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11. Bhatnagar, D.; Roskoski, R. Jr.; Rosendahl, M. S.; Leonard, N. J. Biochemistry 1983, 22, 6310.
12. 50 values were determined from the inhibition curve.
13. Segel, I. H. In Enzyme kinetics; Wiley:New York, 1975; p 106.
14. m = 10 μM for ATP was used in the calculation.
15. Bramson, H. N.; Thomas, N.; DeGrado, W. F.; Kaiser, E. T. J. Am. Chem. Soc. 1980, 102, 7156.
16. 9-(2-(2-(2-(2-Tetrahydropyranyloxy)ethoxy)ethoxy)ethyl)adenine was prepared via alkylation of the adenine anion.