Cyclic nucleotide esterification: relationship to phosphate ring geometry and growth regulation in synchronized human lymphocytes. |
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Authors: | G Forrest A J Millis A P Whipple |
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Institution: | 1. Spectroscopy Laboratory, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 U.S.A.;2. Department of Biological Sciences, State University of New York at Albany, Albany, New York 12222 U.S.A.;3. Department of Pediatrics, Albany Medical College, Albany, New York 12208 U.S.A. |
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Abstract: | Infrared spectra of neutral aqueous solutions of nucleoside 3′,5′-cyclic monophosphates indicate an increase in the antisymmetric phosphoryl stretching frequency to 1236 cm?1 from 1215 cm?1 in trimethylene cyclic phosphates. A further increase to 1242 cm?1 accompanies esterification of the 2′-ribose hydroxyl. The O2′-esterified and 2′-deoxy cyclic nucleotides examined display both reduced kinase binding and altered phosphoryl stretching frequencies, suggesting that modification of the phosphate ring represents a common feature in decreased kinase activation. Reversible inhibition of mitosis in thymidine-synchronized human lymphocytes by 2 mmN6,O2′-dibutyryladenosine 3′,5′-cyclic monophosphate and N6-monobutyryladenosine 3′,5′-cyclic monophosphate was observed. However, adenosine 3′,5′-cyclic monophosphate, O2′-monobutyryladenosine 3′,5′-cyclic monophosphate, butyric acid, and ethyl butyrate had no effect on mitosis when present at 2 mm concentrations during S and G2. These results are consistent with hydrolysis of O2′-monobutyryladenosine 3′,5′-cyclic monophosphate and adenosine 3′,5′-cyclic monophosphate by esterase and phosphodiesterase enzymes and suggest that modification of the N6 amino group is necessary for the antimitotic activity of N6,O2′-dibutyryladenosine 3′, 5′-cyclic monophosphate. |
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