title: Inhibition of human DNA ligase by anthracyclines and distamycins.
abstract: Antitumor anthracyclines and distamycins behave as strong inhibitors of human replicative DNA ligase. The enzyme appears sensitive to a specific occupancy of the minor groove of DNA. Inhibition by anthracyclines takes place after enzyme adenylation, does not correlate with DNA unwinding potency but strictly correlates with the presence of an amino group on the sugar. In contrast to the non-toxic distamycin A, its antitumor derivative FCE24517 inhibits DNA joining, enzyme adenylation and AMP-driven DNA topoisomerisation. Our data favour a model in which multiple enzymic targets contribute to the activity of these antitumor drugs.
authors.affiliation: Istituto di Genetica Biochimica ed Evoluzionistica, CNR, Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ciarrocchi
authors.forename: M
authors.initials: M
authors.lastname: Fontana
authors.forename: S
authors.initials: S
authors.lastname: Spadari
authors.forename: A
authors.initials: A
authors.lastname: Montecucco
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D011088:DNA Ligases / Q000037:antagonists & inhibitors*; D004214:Distamycins / Q000494:pharmacology*; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000903:Antibiotics, Antineoplastic; D004214:Distamycins; D004247:DNA; D011088:DNA Ligases