Synthesis and resistance to enzymic hydrolysis of stereochemically-defined phosphonate and thiophosphate analogues of P1,P4-bis(5'-adenosyl) tetraphosphate.
Novel analogues of P1,P4-bis(5'-adenosyl) tetraphosphate, Ap4A (1), have been prepared with sulphur substituents at P1 and P4 and either oxygen or methylene bridges at the P2,P3-position. Separation of three isomers of the ApspCH2ppsA species has been achieved by a combination of mplc and hplc and the Rp,Rp, Rp,Sp, and Sp,Sp diastereoisomers identified on the basis of selective enzymatic hydrolysis using snake venom phosphodiesterase. Each of these three isomers is a strong competitive inhibitor of the specific Ap4Aase from Artemia and is highly resistant to the asymmetric cleavage normally catalysed by this enzyme.
Blackburn
G M
GM
Department of Chemistry, University of Sheffield, UK.
Taylor
G E
GE
Thatcher
G R
GR
Prescott
M
M
McLennan
A G
AG
D000227:Adenine Nucleotides / Q000138:chemical synthesis*; D015226:Dinucleoside Phosphates; D006868:Hydrolysis; D007202:Indicators and Reagents; D007536:Isomerism; D007700:Kinetics; D063065:Organophosphonates / Q000138:chemical synthesis*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D013329:Structure-Activity Relationship
D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D007202:Indicators and Reagents; D063065:Organophosphonates; C020733:diadenosine tetraphosphate; D010727:Phosphoric Diester Hydrolases