ISSN:
1042-7163
Schlagwort(e):
Chemistry
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Chemie und Pharmazie
Notizen:
The enzymatic cleavage of a scissile P—O bond can be blocked by recourse to phosphonate analogues of biological phosphate esters. α-Fluorophosphonates have an enhanced electronegativity at the bridging carbon, which, in many cases, makes them superior to simple methylene phosphonates for the study of enzyme reactions. Thus, the β,γ-difluoro-methylene analogue of ATP is a good substrate for the interferon-induced (2→5)An synthetase, which converts it into a (2→5)A4 species having a 5′-β,γ-difluoromethylenetriphosphate. This binds strongly to RNase L but does not activate it. The unsymmetrical Ap4Aases from Artemia and Lupin are strongly inhibited by P1,P4-dithiophosphate analogues of diadenosyl-5′,5‴-P1,P4-tetraphosphate although nonregiospecific cleavage of certain P2,P3-methylene analogues can be observed. Some of these analogues are remarkably effective inhibitors of platelet aggregation and are effective inhibitors in vivo of arterial blood-clotting in rabbits. Separation of all diastereoisomers of P1,P4-dithiophosphate analogues of Ap4A is achieved cleanly using reverse-phase hplc chromatography and this provides direct access to β,γ-CHF-bridged analogues of ATP with resolved stereochemistry at the CHF center. Lastly, growing cells of Dictyostelium discoideum not only tolerate a range of substituted methylene bisphosphonates in their growth medium but actually incorporate them into nucleotide analogues of ATP and Ap4A.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1002/hc.520020118
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