Phosphonate and thiophosphate nucleotide analogues in studies of some enzyme reactions.
Nucleic Acids Symp Ser
; (22): 125-6, 1990.
Article
em En
| MEDLINE
| ID: mdl-2101893
ABSTRACT
Enzymes which cleave P-O bonds can be blocked by phosphonate analogues of biological phosphates. alpha-Fluorophosphonates are more electronegative at the bridging carbon than simple methylenephosphonates which improves their use for the study of enzymes. Thus, the beta,gamma-difluoromethylene analogue of ATP is a viable substrate for (2----5)An synthetase which converts it into (2----5)An species having a 5'-beta,gamma-difluoromethylene-trisphosphate. This binds strongly to RNase L but does not activate it. The unsymmetrical Ap4Aases from Artemia and lupin are strongly inhibited by P2,P3-fluoromethylenebisphosphonate- and by P1,P4-dithiophosphate-analogues of diadenosyl-5',5"-P1,P4-tetraphosphate while anomalous, non-regiospecific cleavage of some P2,P3-bridged mimics is observed. Certain such analogues inhibit both platelet aggregation in vitro and arterial blood-clotting in rabbits. Separation of the diastereo-isomers of P1,P4-dithiophosphate analogues of Ap4A is achieved using reverse-phase hplc which provides direct access to beta,gamma-CHF-bridged analogues of ATP with resolved stereochemistry at the CHF centre.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatos
/
Enzimas
/
Organofosfonatos
/
Nucleotídeos
Idioma:
En
Revista:
Nucleic Acids Symp Ser
Ano de publicação:
1990
Tipo de documento:
Article
País de afiliação:
Reino Unido