Document 0800
 DOCN  M94B0800
 TI    Effects of novel anti-viral adenosine analogues on the activity of
       S-adenosylhomocysteine hydrolase from human liver.
 DT    9412
 AU    Fabianowska-Majewska K; Duley JA; Simmonds HA; Purine Research
       Laboratory, UMDS Guy's Hospital, London, U.K.
 SO    Biochem Pharmacol. 1994 Aug 30;48(5):897-903. Unique Identifier :
       AIDSLINE MED/94380105
 AB    Some adenosine analogues have been found previously to inhibit
       S-adenosylhomocysteine (SAH)-hydrolase activity in erythrocyte lysates.
       In this study, the enzyme was purified 500-fold from human liver and its
       M(r) found to be 190,000. Its kinetics in the synthase direction were
       studied, the Km for adenosine being determined as 32 microM. Several
       purine nucleoside analogues currently used in antitumour and antiviral
       therapy were tested for their influence on SAH-hydrolase activity. The
       results confirmed our previous findings for the unpurified human
       erythrocyte enzyme, and demonstrated that the most potent inhibitors of
       human liver SAH-hydrolase were neplanocin A, 7-deaza-adenosine
       (tubercidin), 2'-deoxyadenosine, and 9-beta-D-arabino-furanosyladenine.
       Analogues showing intermediate inhibition were 2'3'-dideoxyadenosine
       (2'3'-ddAdo), 5'-deoxy-5'-methyl-thioadenosine, 3'-deoxy-adenosine,
       2-chloroadenosine, 1,2,4-triazole-3-carboxamide riboside (ribavirin),
       delta-adenosylornithine (sinefungin), S-adenosylmethionine,
       5-amino-4-imidazole carboxamide riboside (AICAR), and
       5'-iodo-5'-deoxyadenosine (5'I,5'-dAdo). Weak or no inhibition was noted
       with 5'-deoxyadenosine, 5-hydroxyimidazole-4-carboxamideriboside
       (bredinin), inosine and its deoxy analogues, and acyclovir. Our results
       show that drugs such as 2'3'-dideoxyadenosine (used in HIV therapy) and
       ribavirin (an inhibitor of inosinate dehydrogenase), in addition to
       their other known mechanisms of action, have an inhibitory effect on
       SAH-hydrolase activity, which may be of significance in their antiviral
       action.
 DE    Adenosine/*ANALOGS & DERIVATIVES/PHARMACOLOGY  Antiviral
       Agents/*PHARMACOLOGY  Human  Hydrolases/*ANTAGONISTS & INHIB/ISOLATION &
       PURIF  Liver/*ENZYMOLOGY  Structure-Activity Relationship  Support,
       Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).