Linked Life Data

2817817

Source:http://linkedlifedata.com/resource/pubmed/id/2817817

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1989-12-8
pubmed:abstractText
Cis-platinum derivatives were observed to inhibit the activity of DNA polymerase alpha of P388 lymphocytic leukemia cells. A 600g nuclear preparation of the polymerase alpha was inhibited by cis-diamminedichloroplatinum(II) [cDDP], diamminemalonatoplatinum(II) [MAL], (1,2-diaminocyclohexane)-dichloroplatinum(II) [DACH-Pt-CL2], and (1,2-diaminocyclohexane)malonato-platinum(II) [DACH-Pt-MAL]. cDDP was a more potent inhibitor of the enzyme activity which was positively correlated with the observed inhibition of DNA synthesis of P388 cells in vivo and in vitro. The inhibition of the 600g preparation by cDDP could be partially reversed by the addition of exogenous ctDNA, but 35% inhibition was not retreivable by adding new template. Isolation of the P388 DNA polymerase alpha enzyme by DEAE column chromatography led to an enzyme with 100 fold purification, which was sensitive to N-ethyl maleimide at 0.1 mM concentration. cDDP inhibited the activity of this enzyme in a dose dependent manner. However, MAL, DACH-Pt-Cl2 and DACH-Pt-MAL afforded no inhibition, nor did the latter two derivatives bind to the enzyme. cDDP inhibition of the activity of purified enzyme was partially reversed by the addition of exogenous ctDNA and by the addition of dGTP, whereas addition of other d(NTP)s had no effect on the recovery of the enzyme activity. These studies suggest that cDDP inhibits DNA polymerase alpha activity and that the inhibition is not the sole mechanism of the action of the drug in suppression of DNA synthesis and cell death. Preliminary studies suggest that the drug may bind to the apoprotein of the enzyme in a competitive manner with dGTP.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0250-7005
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
915-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
The inhibition of P338 lymphocytic leukemia DNA polymerase alpha activity by cis-diamminedichloroplatinum(II) and related derivatives.
pubmed:affiliation
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.