Synthesis and resistance to enzymic hydrolysis of stereochemically-defined phosphonate and thiophosphate analogues of P1,P4-bis(5'-adenosyl) tetraphosphate.

G. M. Blackburn; G. E. Taylor; G. R. Thatcher; M. Prescott; A. G. McLennan

doi:10.1093/nar/15.17.6991

Synthesis and resistance to enzymic hydrolysis of stereochemically-defined phosphonate and thiophosphate analogues of P1,P4-bis(5'-adenosyl) tetraphosphate.

G. M. Blackburn
, G. E. Taylor
, G. R. Thatcher
, M. Prescott
, A. G. McLennan

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	6991-7004
Number of pages	14
Journal	Nucleic acids research
Volume	15
Issue number	17
DOIs	https://doi.org/10.1093/nar/15.17.6991
State	Published - 1987
Externally published	Yes

ASJC Scopus subject areas

Genetics

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title = "Synthesis and resistance to enzymic hydrolysis of stereochemically-defined phosphonate and thiophosphate analogues of P1,P4-bis(5'-adenosyl) tetraphosphate.",

abstract = "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.",

author = "Blackburn, \{G. M.\} and Taylor, \{G. E.\} and Thatcher, \{G. R.\} and M. Prescott and McLennan, \{A. G.\}",

note = "Funding Information: We thank the SERC for financial support through a CASE Studentship (to G.E.T.) and Research Grants GR/D/35438 (to G.M.B.) and GR/E/26358 (to A.G.McL). The generous support of the North West Cancer Research Fund and of the Royal Society (to A.G.McL.) is also acknowledged.",

year = "1987",

doi = "10.1093/nar/15.17.6991",

language = "English (US)",

volume = "15",

pages = "6991--7004",

journal = "Nucleic acids research",

issn = "0305-1048",

publisher = "Oxford University Press",

number = "17",

}

TY - JOUR

T1 - Synthesis and resistance to enzymic hydrolysis of stereochemically-defined phosphonate and thiophosphate analogues of P1,P4-bis(5'-adenosyl) tetraphosphate.

AU - Blackburn, G. M.

AU - Taylor, G. E.

AU - Thatcher, G. R.

AU - Prescott, M.

AU - McLennan, A. G.

N1 - Funding Information: We thank the SERC for financial support through a CASE Studentship (to G.E.T.) and Research Grants GR/D/35438 (to G.M.B.) and GR/E/26358 (to A.G.McL). The generous support of the North West Cancer Research Fund and of the Royal Society (to A.G.McL.) is also acknowledged.

PY - 1987

Y1 - 1987

N2 - 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.

AB - 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.

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AN - SCOPUS:0023651234

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JO - Nucleic acids research

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IS - 17

ER -

Synthesis and resistance to enzymic hydrolysis of stereochemically-defined phosphonate and thiophosphate analogues of P1,P4-bis(5'-adenosyl) tetraphosphate.

Abstract

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