Molecular origins of selectivity in the interaction of amsacrine-4-carboxamide with GC-rich sequences in DNA.
To determine the molecular origins of the preferential binding of an antitumour amsacrine-4-carboxamide derivative to GC-rich sequences in DNA, we have used the polymerase chain reaction to synthesize a series of oligodeoxynucleotides in which the position of the purine 2-amino group is varied and then investigated the binding of the drug to normal and modified DNA molecules by means of DNase I footprinting. The results indicate that the 2-amino group of guanine represents an important but not unique element which directs selective binding of amsacrine-4-carboxamides to GC-rich sequences.
Bailly
C
C
Institut de Recherches sur le Cancer, INSERM Unité 124, Lille, France.
Denny
W A
WA
Waring
M J
MJ
D000677:Amsacrine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001345:Autoradiography; D003562:Cytidine; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D018983:DNA Footprinting; D004926:Escherichia coli; D006147:Guanine; D010957:Plasmids
D000970:Antineoplastic Agents; C104094:SN 16713; D000677:Amsacrine; D003562:Cytidine; D006147:Guanine; D004247:DNA