CORRELATION BETWEEN ANTHRACYCLINE STRUCTURE AND HUMAN DNA-LIGASE INHIBITION

被引:18
作者
CIARROCCHI, G
LESTINGI, M
FONTANA, M
SPADARI, S
MONTECUCCO, A
机构
[1] Istit. di Genetica Biochimica, ed Evoluzionistica, C.N.R., I-27100 Pavia
关键词
D O I
10.1042/bj2790141
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A total of 19 anthracycline derivatives were tested for their ability to interfere in vitro with the action of the human replicative DNA ligase. Only those with the sugar devoid of unmodified amino groups or with large configurational modifications were found to be inactive. Maximal inhibition of DNA-joining activity was found to require a 4'-deoxy-3'-amino sugar. Self-adenylation of DNA ligase was largely insenstive to these drugs. An important general finding is that slight modifications of the anthracycline structure have pronounced effects on DNA-ligase-inhibitory activity and might be related to the specificity of anthracycline anti-tumour activity.
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页码:141 / 146
页数:6
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