Structures of the adducts formed between [Pt(dien)C1]C1 and DNA<i>in vitro</i>

Johnson, Neil P.; Macquet, Jean‐Pierre; Wiebers, J. L.; Monsarrat, Bernard

doi:10.1093/nar/10.17.5255

Cited by 56 publications

(18 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The glycosyl linkage of guanine residues modified at the N7 position by the monofunctional platinum derivative dienPt is more resistant to acid hydrolysis than that of the unmodified residues (Johnson, 1982;Johnson et al, 1982). We have studied the relative stability of glycosyl linkages of guanine residues modified by cisPt.…”

Section: Nature Of the Adductsmentioning

confidence: 99%

Reaction of cis-diamminedichloroplatinum (II) and DNA in B or Z conformation.

Malinge¹,

Leng²

1984

The EMBO Journal

View full text Add to dashboard Cite

The nature of the adducts and the conformational changes produced in poly(dG‐m5dC).poly(dG‐m5dC) by cis‐diamminedichloroplatinum(II) (cisPt) have been studied. In the reaction of cisPt and B‐DNA, the main adduct is bidentate and arises from an intrastrand cross‐link between two guanine residues separated by a cytosine. This was deduced from the study of the compounds by t.l.c. after acid hydrolysis of the polymer. The platinated polymer is not digested by S1 nuclease. The antibodies to Z‐DNA bind to the platinated polymer with a smaller affinity than to poly (dG‐br5dC).poly(dG‐br5dC). The c.d. spectrum differs from that of poly(dG‐br5dC).poly(dG‐br5dC) or poly(dG‐m5dC).poly‐(dG‐m5dC) in Z conformation. It is concluded that the bidentate adduct induces a conformational change from the B form towards a distorted Z form. In the reaction of cisPt and Z‐DNA, a monodentate adduct is formed. This adduct stabilizes the Z conformation as shown by c.d. and binding to the anti‐Z‐DNA antibodies. At room temperature, the second function of the drug can still react with small ligands such as NH4HCO3. By heating, the second function reacts with a guanine residue. A bidentate adduct is formed as in the reaction of cisPt and B‐DNA and it induces a transition from the Z form to the distorted Z form.

show abstract

Section: Nature Of the Adductsmentioning

confidence: 99%

Reaction of cis-diamminedichloroplatinum (II) and DNA in B or Z conformation.

Malinge¹,

Leng²

1984

The EMBO Journal

View full text Add to dashboard Cite

show abstract

“…In support of this idea, Brouwer et al (1981) have found that cisplatin strongly favors G.C to T.A transversions among 650 nonsense mutations produced in the lacI gene of Escherichia coli, supporting the idea that what is occurring is depurination followed by bypass repair. Pt(dien)CIappears to strengthen the glycosyl bond when it complexes with the N7 position of guanine (Johnson, 1982;Johnson et al, 1982). However, as these authors themselves point out, 'The enhanced biological activities of cis-PDD compared with trans-PDD and [Pt(dien)Cl]Cl are a consequence of different platinum-DNA adducts formed by these compounds in vivo'.…”

Section: Introductionmentioning

confidence: 99%

The primary mode of binding of cisplatin to a B-DNA dodecamer: C-G-C-G-A-A-T-T-C-G-C-G.

Wing¹,

Pjura²,

Drew³

et al. 1984

The EMBO Journal

View full text Add to dashboard Cite

When cisplatin [cis‐ diamminodichloroplatinum (II)] is diffused into pre‐grown crystals of the B‐DNA double‐helical dodecamer C‐G‐C‐G‐A‐A‐T‐T‐C‐G‐C‐G, it binds preferentially to the N7 positions of guanines, with what probably is an aquo bridge between Pt and the adjacent O6 atom of the same guanine. The entire guanine ring moves slightly toward the platinum site, into the major groove. Only three of the eight potential cisplatin binding sites on guanines actually are occupied, and this differential reactivity can be explained in terms of the relative freedom of motion of guanines toward the major groove. This shift of guanines upon ligation may weaken the glycosyl bond and assist in the depurination that leads to mismatch SOS repair and G.C. to T.A. transversion.

show abstract

“…The binding to the latter residues is, however, noticeably slower than to other DNA base residues, and in general the DNA binding of Com2 is slower than that of Com1. Thus, these results suggest that Com1 and Com2 bind to different base residues in DNA and have different base sequence preferences than their simpler analogs cisplatin or [Pt-Cl(dien)]Cl, which both bind preferentially to guanine residues, and cisplatin to a less extent to adenine residues (Johnson et al, 1982, Fichtinger-Schepman et al, 1985Eastman, 1987).…”

Section: Resultsmentioning

confidence: 93%

DNA Interactions of New Antitumor Aminophosphine Platinum(II) Complexes

et al. 1999

View full text Add to dashboard Cite

Mechanistic studies are presented of a novel class of aminophosphine platinum(II) complexes as potential anticancer agents. These new agents, which have demonstrated activity against murine and human tumor cells including those resistant to cisplatin are cis-[PtCl2(Me2N(CH2)3PPh2-P)2] (Com1) and cis-[PtCl(C6H11NH(CH2)2PPh2-N,P)(C6H11NH(CH2) 2PPh2-P)] (Com2). We studied modifications of natural and synthetic DNAs in cell-free media by Com1 and Com2 by various biomedical and biophysical methods and compared the results with those obtained when DNA was modified by cisplatin. The results indicated that Com1 and Com2 coordinated to DNA faster than cisplatin. Bifunctional Com1 formed DNA adducts coordinating to single adenine or guanine residues or by forming cross-links between these residues. In comparison with cisplatin, Com1 formed the adducts more frequently at adenine residues and also formed fewer bidentate lesions. The monofunctional Com2 only formed DNA monodentate adducts at guanine residues. In addition, Com1 terminated DNA synthesis in vitro more efficiently than cisplatin whereas Com2 blocked DNA synthesis only slightly. DNA unwinding studies, measurements of circular dichroism spectra, immunochemical analysis, and studies of the B-Z transition in DNA revealed conformational alterations induced by the adducts of Com1, which were distinctly different from those induced by cisplatin. Com2 had little influence on DNA conformation. It is suggested that the activity profile of aminophosphine platinum(II) complexes, which is different from that of cisplatin and related analogs, might be associated with the specific DNA binding properties of this new class of platinum(II) compounds.

show abstract

Structures of the adducts formed between [Pt(dien)C1]C1 and DNAin vitro

Cited by 56 publications

References 14 publications

Reaction of cis-diamminedichloroplatinum (II) and DNA in B or Z conformation.

Reaction of cis-diamminedichloroplatinum (II) and DNA in B or Z conformation.

The primary mode of binding of cisplatin to a B-DNA dodecamer: C-G-C-G-A-A-T-T-C-G-C-G.

DNA Interactions of New Antitumor Aminophosphine Platinum(II) Complexes

Contact Info

Product

Resources

About