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1990 (1)
1988 (1)
1Author    Ryszard Stolarski, Piotr Lassota, Zygmunt Kazimierczuk, David ShugarRequires cookie*
 Title    Solution Conformations of Some Acyclo Nucleoside and Nucleotide Analogues of Antiviral Acyclonucleosides, and Their Substrate/Inhibitor Properties in Several Enzyme Systems  
 Abstract    Chemical and enzymatic procedures have been employed for the preparation of various phos-phorylated derivatives of the acyclonucleoside 9-(l,3-dihydroxy-2-propoxymethyl)adenine, an analogue of the active antiviral agent 9-(l,3-dihydroxy-2-propoxymethyl)guanine (DHPG). In combination with the previously reported 2',3'-seco nucleosides and their phosphates and cyclic phosphates (Stolarski et al., this made available a broad class of acyclonucleosides and nucleotides, the acyclic moieties of which are capable of mimicing the ribose and 2'-deoxyribose rings. The solution conformations of the foregoing were determined with the aid of 'H, 13 C and 31 P NMR, and compared with those of DHPG and 9-(hydroxyethoxymethyl)guanine (Acyclovir, ACV). Particular attention was devoted to conformations about C-O bonds in different acyclic fragments, which demonstrated well-defined differences between 2',3'-seco derivatives on the one hand (conformational "rigidity") and derivatives with DHP and AC acyclic chains on the other (rotation about the C(l')-0(4') bond). The overall results are in good general agreement with reported crystal structures, and are compared with those obtained by quantum mechanical calcu-lations. The conformational features of the various compounds are also discussed in relation to their substrate and/or inhibitor properties in a number of enzyme systems, including adenosine deamin-ase, phosphodiesterases, nuclease PI, 3'-nucleotidase and herpes virus type 1 thymidine kinase. Abbreviations: AC, 2-hydroxyethoxymethyl; DHP, 1,3-di-hydroxy-2-propoxymethyl; seco, 2',3'-seco or 1,5-dihydro-4-hydroxymethyl-3-oxapentyl-2-[R]; ACV, Acyclovir or AcycloG, 9-(2-hydroxyethoxymethyl)guanine; ACVMP, monophosphate of ACV; AC-Cyt, l-(2-hydroxyethoxy-methyl)cytosine, with similar connotations for AC-Ade and AC-Ura; DHPG, 9-(l,3-dihydroxy-2-propoxymethyl)-guanine; DHP-Ade, adenine analogue of DHPG; DHPGMP, monophosphate of DHPG; DHP-AdeMP, monophosphate of DHP-Ade; DHP-Ade-diP, 3',5'-diphosphate of DHP-Ade; DHP-Ade-3' : 5'-cMP, the 3':5'-cyclic monophosphate of DHP-Ade; secoA, 2',3'-secoadenosine or 9-(l,5-dihydro-4-hydroxymethyl-3-oxa-pentyl-2-[R])adenine, with similar connotations for other acyclonucleosides; seco-5'-GMP, 5'-monophosphate of secoG, and similarly for seco-5'-CMP and seco-5'-AMP; secoC-3' :5'-cMP, 2',3'-secocytidine-3' :5'-cyclic phos-phate, and similarly for secoA-3':5'-cMP; TK, thymidine kinase; cPDase, cyclic nucleotide phosphodiesterase. For purposes of simplicity, the abbreviated terms are used in the text, with the carbon atoms of the acyclic chains numbered as for the corresponding carbon atoms of the pentose ring, as shown in Scheme 1. 
  Reference    Z. Naturforsch. 43c, 231—242 (1988); received December 3 1987 
  Published    1988 
  Keywords    Acyclonucleosides, Phosphates, Cyclic Phosphates, Solution Conformations, Substrate/Inhibitor Properties 
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 TEI-XML for    default:Reihe_C/43/ZNC-1988-43c-0231.pdf 
 Identifier    ZNC-1988-43c-0231 
 Volume    43 
2Author    Ryszard Stolarskia, JaroslawM. Cieslab, David ShugarabRequires cookie*
 Title    Monophosphates and Cyclic Phosphates of Some Antiviral Acyclonucleosides: Synthesis, Conformation and Substrate/Inhibitor Properties in Some Enzyme Systems  
 Abstract    Chemical and enzymatic procedures are described for the synthesis o f the m onophosphates and cyclic phosphates o f the antiviral acyclonucleoside 9-(1,3-dihydroxy-2-propoxym ethyl)-guanine (D H PG), its 3-hydroxymethyl-4-hydroxybutyl analogue, the (/?)-and (S)-epimers o f 9-(3,4-dihydroxybutyl)guanine, and 9-(2,3-dihydroxypropyl)guanine. The structures, and some conform ational features, o f all the foregoing, were determined by 'H and 3IP N M R spectroscopy. Their substrate/inhibitor properties have been examined in several enzyme systems, including ribonucleases, snake venom phosphodiesterase, beef heart and higher plant cyclic nucleotide phosphodiesterases, nuclease P I, and 3'-and 5'-nucleo-tidases. The enzymatic results are considered in relation to the mechanism o f the antiviral ac­ tivity o f the cyclic phosphate o f D H PG . 
  Reference    Z. Naturforsch. 45c, 293 (1990); received October 31 1989 
  Published    1990 
  Keywords    Acyclonucleosides, M onophosphates, Cyclic Phosphates, Conformation, Substrate/Inhibitor Properties 
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 TEI-XML for    default:Reihe_C/45/ZNC-1990-45c-0293.pdf 
 Identifier    ZNC-1990-45c-0293 
 Volume    45