tailieunhanh - Báo cáo khoa học: Methylene analogues of adenosine 5¢-tetraphosphate Their chemical synthesis and recognition by human and plant mononucleoside tetraphosphatases and dinucleoside tetraphosphatases

Adenosine 5¢-polyphosphates have been identified in vitro, as products of certain enzymatic reactions, andin vivo. Although the biological role of these compounds is not known, there exist highly specific hydrolases that degrade nucleoside 5¢-polyphosphates into the corresponding nucleoside 5¢-triphos-phates. | ềFEBS Journal Methylene analogues of adenosine 5 -tetraphosphate Their chemical synthesis and recognition by human and plant mononucleoside tetraphosphatases and dinucleoside tetraphosphatases Andrzej Guranowski1 Elzbieta Starzynska1 Matgorzata Pietrowska-Borek1 Jacek Jemielity2 Joanna Kowalska2 Edward Darzynkiewicz2 Mark J. Thompson3 and G. Michael Blackburn3 1 Department of Biochemistry and Biotechnology AgriculturalUniversity Poznan Poland 2 Department of Biophysics Institute of ExperimentalPhysics Warsaw University Poland 3 Department of Chemistry Krebs Institute University of Sheffield UK Keywords adenosine 5 -tetraphosphate p4A methylene analogues of p4A nucleoside tetraphosphatase dinucleoside tetraphosphatase Correspondence A. Guranowski Katedra Biochemii i Biotechnologii Akademia Rolnicza ul. Wotyiiska 35 60-637 Poznan Poland Fax 48 61 8487146 Tel 48 61 8487201 E-mail guranow@ Website http Note This study is dedicated to Professor Wojciech J. Stec on the occasion of his 65th birthday. Received 9 November 2005 revised 15 December 2005 accepted 21 December 2005 doi Adenosine 5 -polyphosphates have been identified in vitro as products of certain enzymatic reactions and in vivo. Although the biological role of these compounds is not known there exist highly specific hydrolases that degrade nucleoside 5 -polyphosphates into the corresponding nucleoside 5 -triphos-phates. One approach to understanding the mechanism and function of these enzymes is through the use of specifically designed phosphonate analogues. We synthesized novel nucleotides a P-methylene-adenosine 5 -tetraphosphate pppCH2pA P y-methylene-adenosine 5 -tetraphosphate ppCH2ppA y ỗ-methylene-adenosine 5 -tetraphosphate pCH2pppA aP yỗ-bismethylene-adenosine 5 -tetraphosphate pCH2ppCH2pA aP Py-bismethylene-adenosine 5 -tetraphosphate ppCH2pCH2pA and by yỗ-bis dichloro methylene-adenosine 5 -tetraphosphate pCCl2pCCl2ppA and tested them as

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