Sequence-dependent conformational changes in DNA induced by polynuclear platinum complexes.
In this work, the B-->Z transition of poly(dG-dC).poly(dG-dC) and the B-->A transition of poly(dG).poly(dC) and of calf thymus (CT) DNA fragments modified by antitumor bifunctional polynuclear platinum complexes were investigated by circular dichroism (CD). The transition from the B- to Z-form of DNA was inducible with all three compounds studied, as indicated by an inversion of the B-form spectra. The B-->A transition in poly(dG).poly(dC) was induced easily by platinum complex binding alone, while the B-->A transition in CT DNA was induced by ethanol but inhibited by coordination of all polynuclear platinum compounds used here. It was shown that the compound [¿cis-PtCl(NH3)2¿2 mu-¿H2N(CH2)6NH2¿] (NO3)2 (1,1/c,c) was most effective at inhibiting the B-->A transition in CT DNA, and [¿trans-PtCl(NH3)2¿2 mu-¿trans-Pt(NH3)2(H2N(CH2)6NH2)2¿] (NO3)4 (1,0,1/t,t,t) was least effective, while the effectiveness of [¿trans-PtCl(NH3)2¿2 mu-¿H2N(CH2)6NH2¿] (NO3)2 (1,1/t,t) fell between the two. This corresponded to the relative amounts of interstrand crosslinks in double-stranded DNA caused by each compound.
McGregor
T D
TD
Department of Chemistry, Virginia Commonwealth University, Richmond 23284-2006, USA.
Balcarová
Z
Z
Qu
Y
Y
Tran
M C
MC
Zaludová
R
R
Brabec
V
V
Farrell
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002942:Circular Dichroism; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011066:Poly C / Q000737:chemistry; D011068:Poly G / Q000737:chemistry; D011089:Polydeoxyribonucleotides / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D009944:Organoplatinum Compounds; D011089:Polydeoxyribonucleotides; D011068:Poly G; C023826:poly(dC); C026628:poly(dG); C019530:poly(dC-dG); D011066:Poly C; D004247:DNA; C114062:BBR 3464; D002945:Cisplatin