Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(Sp)-2'-Deoxyadenosine 5'-O-[1-17O,1-18O,1,2-18O]triphosphate has been synthesized by desulfurization of (Sp)-2'-deoxyadenosine 5'-O-(1-thio[1,1-18O2]diphosphate) with N-bromosuccinimide in [17O]water, followed by phosphorylation with phosphoenolpyruvate-pyruvate kinase. A careful characterization of the product using high-resolution 31P NMR revealed that the desulfurization reaction proceeded with approximately 88% direct in-line attack at the alpha-phosphorus and 12% participation by the beta-phosphate to form a cyclic alpha,beta-diphosphate. The latter intermediate underwent hydrolysis by a predominant nucleophilic attack on the beta-phosphate. This complexity of the desulfurization reaction, however, does not affect the stereochemical integrity of the product but rather causes a minor dilution with nonchiral species. The usefulness of the (Sp)-2'-deoxyadenosine 5'-O-[1-17O,1-18O,1,2-18O]triphosphate in determining the stereochemical course of deoxyribonucleotidyl-transfer enzymes is demonstrated by using it to delineate the stereochemical course of the 3'----5'-exonuclease activity of DNA polymerase I. Upon incubation of this oxygen-chiral substrate with Klenow fragment of DNA polymerase I in the presence of poly[d(A-T)] and Mg2+, a quantitative conversion into 2'-deoxyadenosine 5'-O-[16O,17O,18O]monophosphate was observed. The stereochemistry of this product was determined to be Rp. Since the overall template-primer-dependent conversion of a deoxynucleoside triphosphate into the deoxynucleoside monophosphate involves incorporation into the polymer followed by excision by the 3'----5'-exonuclease activity and since the stereochemical course of the incorporation reaction is known to be inversion, it can be concluded that the stereochemical course of the 3'----5'-exonuclease is also inversion.
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PMID:Stereochemical course of the 3'----5'-exonuclease activity of DNA polymerase I. 609 2

5'-Deoxy-5'-methylthioadenosine inhibits Concanavalin A induced rat T lymphocyte proliferation in a dose dependent manner (50 microM to 1000 microM). The extent of inhibition by MTA of lymphocyte proliferation was greatest when MTA was added to the cells at the same time as Concanavalin A. The determination of cyclic AMP level from 30 min to the 6th hour shows that 5'-Deoxy-5'-methylthioadenosine inhibition is correlated with an elevation of cyclic AMP at this mitogen recognition phase. 5'-Deoxy-5'-methylthioadenosine concentrations that inhibit rat T lymphocyte proliferation also inhibit phosphodiesterase activity. This biochemical mechanism could be specific to 5'-Deoxy-5'-methylthioadenosine inhibition since in an another model of inhibition of rat T lymphocyte proliferation (2'-Deoxyadenosine 10 microM, in adenosine deaminase deficiency conditions: 2'-Deoxycoformycin 10 microM), no significant modification of cyclic AMP level can be demonstrated.
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PMID:5'-Deoxy-5'-methylthioadenosine inhibition of rat T lymphocyte phosphodiesterase: correlation with inhibition of Con A induced proliferation. 630 88