Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dinucleoside 5',5"'- P (1), P ( n )-polyphosphates, and particularly the diadenosine compounds, have been implicated in extracellular purinergic signalling and in various intracellular processes, including DNA metabolism, tumour suppression and stress responses. If permitted to accumulate, they may also be toxic. One approach to understanding their function is through the various specific degradative enzymes that regulate their levels. Eight adenosine-5'- O -phosphorylated polyols (derivatives of glycerol, erythritol and pentaerythritol) and 11 adenosine-5'- O -phosphorothioylated polyols (derivatives of glycerol, erythritol, pentaerythritol, butanediol and pentanediol) have been tested as inhibitors of specific diadenosine tetraphosphate (Ap(4)A) hydrolases. Of these two groups of novel nucleotides, the adenosine-5'- O -phosphorothioylated polyols were generally stronger inhibitors than their adenosine-5'- O -phosphorylated counterparts. 1,4-Di(adenosine-5'- O -phosphorothio) erythritol appeared to be the strongest inhibitor of ( asymmetrical ) Ap(4)A hydrolases (EC 3.6.1.17) from both lupin and human, with K (i) values of 0.15 microM and 1.5 microM respectively. Of eight adenosine-5'- O -phosphorylated polyols, 1,4-di(adenosine-5'- O -phospho) erythritol was the only compound that inhibited the lupin enzyme. Two derivatives of pentaerythritol, di(adenosine-5'- O -phosphorothio)-di(phosphorothio) pentaerythritol and tri(adenosine-5'- O -phosphorothio)-phosphorothio-pentaerythritol, proved to be the strongest inhibitors of the prokaryotic ( symmetrical ) Ap(4)A hydrolase (EC 3.6.1.41) so far reported. The estimated K (i) values were 0.04 microM and 0.08 microM respectively. All of these inhibitors were competitive with respect to Ap(4)A. These new selectively acting Ap(4)A analogues should prove to be valuable tools for further studies of Ap(4)A function and of the enzymes involved in its metabolism.
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PMID:Adenosine-5'-O-phosphorylated and adenosine-5'-O-phosphorothioylated polyols as strong inhibitors of (symmetrical) and (asymmetrical) dinucleoside tetraphosphatases. 1269 25

In this paper, we describe the synthesis of the 3'-3'-linked oligonucleotides connected with pentaerythritol composed of asymmetrical sequences. Stability of the triplexes between these oligonucleotides and the DNA targets involving the adjacent oligopurine domains on alternate strands was investigated using the electrophoretic mobility shift assay (EMSA) and DNase I footprinting experiment. It was found that the 3'-3'-linked oligonucleotides composed of asymmetrical sequences formed the stable antiparallel triplexes with the DNA targets as compared with the unlinked oligonucleotides. Thus, oligonucleotides linked with pentaerythritol would be useful as antigene oligonucleotides for DNA targets consisting of the alternating oligopyrimidine-oligopurine sequences.
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PMID:Nucleosides and nucleotides. Part 226: alternate-strand triple-helix formation by 3'-3'-linked oligodeoxynucleotides composed of asymmetrical sequences. 1514 1