ISSN:
1573-4943
Keywords:
cyclic AMP derivatives
;
affinity labels
;
chemical modification of enzymes
;
nucleotide affinity labels
;
cAMP phosphodiesterase
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The syntheses of two potential cAMP affinity lables, 1,N 6-(3-iodopropyleno)adenosine 3′,5′-cyclic-monophosphate and 2′-O-(2-iodo-3-hydroxypropyl) adenosine 3′,5′-cyclic-monophosphate, by a two-step chemical procedure are described. TheN 6- and 2′-O-allyl intermediates were prepared selectively by alkylation of cAMP in organic and alkaline aqueous solutions, respectively. Treatment of theN 6-allyl derivative withN-iodosuccinimide resulted in iodine addition to the double bond and cyclization to theN 1 position of the purine ring. The iodohydrin analog was synthesized by reaction of 2′-O-allyl-cAMP with potassium iodide and thallium trichloride in acetate buffered solution. The products were isolated by column chromatography and characterized by thin-layer chromatography, elemental analysis, and ultraviolet,13C, and1H NMR spectroscopy. The cAMP analogs were found to react with lysine and cysteine. Both cAMP derivatives were tested for their reaction with the low-K m cAMP phosphodiesterase of human platelets. The ribose-substituted analog functioned as a competitive inhibitor (K I =0.72 μM) and caused a time-dependent irreversible inactivation of the phosphodiesterase. In contrast, the purine-substituted derivative acted neither as a reversible competitive inhibitor nor as an irreversible inactivator of the enzyme. These results indicate the specificity of these potential cAMP analogs in their interaction with the phosphodiesterase.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01025376
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