Effects of novel anti-viral adenosine analogues on the activity of S-adenosylhomocysteine hydrolase from human liver

Fabianowskamajewska, K, Duley, JA and Simmonds, HA (1994) Effects of novel anti-viral adenosine analogues on the activity of S-adenosylhomocysteine hydrolase from human liver. Biochemical Pharmacology, 48 5: 897-903. doi:10.1016/0006-2952(94)90360-3


Author Fabianowskamajewska, K
Duley, JA
Simmonds, HA
Title Effects of novel anti-viral adenosine analogues on the activity of S-adenosylhomocysteine hydrolase from human liver
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 1994-01-01
Year available 1994
Sub-type Article (original research)
DOI 10.1016/0006-2952(94)90360-3
Open Access Status Not yet assessed
Volume 48
Issue 5
Start page 897
End page 903
Total pages 7
Place of publication OXFORD
Publisher PERGAMON-ELSEVIER SCIENCE LTD
Language eng
Subject 3004 Pharmacology
Abstract 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 was studied, the K-m for adenosine being determined as 32 mu M. Several purine nucleoside analogues currently used in anti-tumour and antiviral therapy was 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'-deoxyadensone, and 9-beta-D-arabino-furanosyladenine. Analogues showing intermediate inhibition were 2'3'-dideoxyadenosine (2'3'-ddAdo), 5'-deoxy-5'-methyl-thioadensoine, 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.
Keyword antiviral drugs
dideoxyadenosine
HIV
neplanocin A
ribavirin
S-adenosylhomocysteine hydrolase
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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