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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1992-2-18
|
| pubmed:abstractText |
Two classes of enzymes, poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferases, catalyze covalent attachment of multiple or single residues, respectively, of the ADP-ribose moiety of NAD+ to various proteins. In order to find good inhibitors of poly(ADP-ribose) synthetase free of side actions and applicable to in vivo studies, we made a large scale survey using an in vitro assay system, and found many potent inhibitors. The four strongest were 4-amino-1,8-naphthalimide, 6(5H)- and 2-nitro-6(5H)-phenanthridinones, and 1,5-dihydroxyisoquinoline. Their 50% inhibitory concentrations, 0.18-0.39 microM, were about two orders of magnitude lower than that of 3-aminobenzamide that is currently most popularly used. A common structural feature among all potent inhibitors, including 1-hydroxyisoquinoline, chlorthenoxazin, 3-hydroxybenzamide, and 4-hydroxyquinazoline, in addition to the four mentioned above, was the presence of a carbonyl group built in a polyaromatic heterocyclic skeleton or a carbamoyl group attached to an aromatic ring. Most of the inhibitors exhibited mixed-type inhibition with respect to NAD+. Comparative studies of the effects on poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase from hen heterophils revealed high specificity of most of the potent inhibitors for poly(ADP-ribose) synthetase. On the other hand, unsaturated long-chain fatty acids inhibited both enzymes, and saturated long-chain fatty acids and vitamin K1 acted selectively on mono(ADP-ribosyl)transferase. The finding of many inhibitors of ADP-ribosyltransferases, especially poly(ADP-ribose) synthetase, supports the view that ADP-ribosylation of proteins may be regulated by a variety of metabolites or structural constituents in the cell.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADP Ribose Transferases,
http://linkedlifedata.com/resource/pubmed/chemical/Acetophenones,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Nonesterified,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/NAD,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Niacinamide,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolines,
http://linkedlifedata.com/resource/pubmed/chemical/acetophenone,
http://linkedlifedata.com/resource/pubmed/chemical/benzamide
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
25
|
| pubmed:volume |
267
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1569-75
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:1530940-ADP Ribose Transferases,
pubmed-meshheading:1530940-Acetophenones,
pubmed-meshheading:1530940-Animals,
pubmed-meshheading:1530940-Benzamides,
pubmed-meshheading:1530940-Cattle,
pubmed-meshheading:1530940-Enzyme Inhibitors,
pubmed-meshheading:1530940-Fatty Acids, Nonesterified,
pubmed-meshheading:1530940-Isoquinolines,
pubmed-meshheading:1530940-Kinetics,
pubmed-meshheading:1530940-NAD,
pubmed-meshheading:1530940-Naphthalenes,
pubmed-meshheading:1530940-Niacinamide,
pubmed-meshheading:1530940-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:1530940-Pyrimidines,
pubmed-meshheading:1530940-Quinazolines,
pubmed-meshheading:1530940-Quinolines,
pubmed-meshheading:1530940-Structure-Activity Relationship,
pubmed-meshheading:1530940-Thymus Gland
|
| pubmed:year |
1992
|
| pubmed:articleTitle |
Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase.
|
| pubmed:affiliation |
Department of Clinical Science and Laboratory Medicine, Kyoto University Faculty of Medicine, Japan.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|