Platination Pathways for Reactions of Cisplatin with GG Single‐Stranded and Double‐Stranded Decanucleotides

Barnham, Kevin J.; Sadler, Peter J.; Berners‐Price, Susan J.; Frenkiel, Thomas A.; Frey, Urban

doi:10.1002/anie.199518741

Cited by 58 publications

(36 citation statements)

References 15 publications

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“…Rate constants for each step were extracted from numerically optimised fits to these data curves and the calculated curves are also shown in Figure 2. Calculated rate constants are listed in Table along with those reported previously for reaction at the GpG site [28,29]. Rates of monofunctional adduct formation at the ApG site are broadly similar to those at the GpG site.…”

Section: Introductionsupporting

confidence: 54%

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Steric Determinants of Pt/DNA Interactions and Anticancer Activity

et al. 1998

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Section: Introductionsupporting

confidence: 54%

“…They also studied the reaction of cisplatin with oligonucleotides and found a higher rate of binding to the 3' guanine of a GpG pair and faster closure to the bifunctional adduct from this base [28,29].…”

Section: Introductionmentioning

confidence: 99%

Steric Determinants of Pt/DNA Interactions and Anticancer Activity

et al. 1998

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“…They detected no aqua monoadduct and found that one chloro monoadduct ring-closed much faster than the other. 1371 The absence of accumulation of aqua monoadducts also indicates that c~~-[P~(NH,),(H,O),]~ + is not the predominant species reacting with DNA under these experimental conditions. In our opinion, it would be premature to extrapolate this result to in vivo conditions.…”

Section: Eic This Conversion Is Expressed By Equations (I)-(iii)mentioning

confidence: 93%

Reactions of the Double‐Stranded Oligonucleotide d(TTGGCCAA)₂withcis‐[Pt(NH₃)₂(H₂O)₂]²⁺and [Pt(NH₃)₃(H₂O)]²⁺

Reeder¹,

Gonnet²,

Kozelka³

et al. 1996

Chemistry A European J

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The kinetics of the reactions between the GGcontaining double-stranded oligonucleotide d(TTGGCCAA), (II) and the platinum complexes cis-[Pt-(Hz0)lz+ (2) were studied and compared with those already determined for the reactions of the single-stranded octanucleotide d(CTGGCTCA) (I).['] The results were as follows: i) Complex 1 reacted faster than 2 with both I and 11. ii) Both complexes 1 and 2 reacted faster with I1 than with I. This acceleration was greater for 1 ( x 13) than for 2 ( x 4) and only due to the increase of the platination rate of the 5'-G of the GG sequence. iii) For both I and 11, the first platination by 1 and ( N H~) Z ( H Z~) Z~~~(1) and [Pt(NH3)3-2 was faster on the 5'-G than on the 3'43. This difference was more significant for the platination of I1 (ks,/k3, = 12 for 1 and 5 for 2) than of I (ks,/k3, 5 2). iv) The cyclization reaction of the monoadducts (G*) of 1 to yield the GG cis-Pt(NH,)$+ chelate (G*G*) was considerably slowed down in the duplex. This rate decrease was significantly larger for the chelation of the 5'-G* (factor of 16) than of the 3'-G* (factor of 4) monoadducts. v) The intrastrand chelation of the 3'-G* monoadducts (k3J was faster than that of the 5'-G* monoadducts ( k 5 J , both for I and I1 (k38c/ks,c = 3 and 13, respectively). vi) In addition to the intrastrand G*G* crosslink, we also observed the interstrand crosslink d(GG*CC)-d(GG*CC) between the two 3'43s of the central tetranucleotide. The rate constant for the interstrand crosslinking (k3,i) was half that of the intrastrand chelation (k3,c).vii) The 5' monoadduct, which was formed faster (ks. > k3.) and was chelated more slowly (k5,c @ k,.i c k3.c), exhibited a half-life of 3.2 h under our experimental conditions.

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“…Reactions of 2 in acidic conditions are complicated by the hydrolysis of 2 to 3 (Scheme 2) and this occurs in parallel with the direct reaction of 2 with the oligonucleotide. Since 3 is considerably more reactive towards nucleobases than 2, [22,23] the commonly used approximation neglecting the reaction between 3 and the oligonucleotide [12,13,16,24] yields unprecise results. Our solution to the problem resided in separate investigations of the reaction of 3 in a series of experiments that we reported earlier [18] (indicated by bold arrows in Schemes 2 and 3) and allowed the reactions of 2 (Scheme 2) and 4 (Scheme 3) to be studied with a reduced number of variables.…”

Section: IImentioning

confidence: 99%

“…Adjustments of pH by addition of diluted HClO 4 by hand or using a pH-stat did not work satisfactorily in our hands, since even very small additions caused significant pH jumps, or the acid had to be so diluted that the volume increase perturbed the measurements. Unlike other authors, [12,13,16,24] we refrained from using phosphate or other buffers, since they contain potential ligands for platinum. [34] Specifically, the frequently used phosphate buffer has been clearly shown to perturb the kinetics of DNA platination reactions.…”

Section: 'mentioning

confidence: 99%

A Complete Kinetic Study of GG versus AG Platination Suggests That the Doubly Aquated Derivatives of Cisplatin Are the Actual DNA Binding Species

et al. 2000

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The hairpin-stabilized double-stranded oligonucleotides d(TATGGTATT4ATACCATA) (I) and d(TATAGTATT4ATACTATA) (II) were allowed to react with the three aquated forms of the antitumor drug cisplatin (cis-[PtCl2(NH3)2], 1) which are likely candidates for DNA binding, that is, cis-[PtC1(NH3)2(H2O)]+ (2), cis-[Pt(NH3)2(H2O)2]2+ (3), and its conjugate base cis-[Pt(OH)(NH3)2(H2O)]+ (4). The reaction between I and [Pt(NH3)3(H2O)]2+ (5) was also studied for comparison. All reactions were monitored by HPLC. The platination reactions of I and II were carried out in NaClO4 (0.1M) at 293 K and at a constant pH of 4.5 +/- 0.1 for 2, 3, and 5. The data relative to the platination by 4 were obtained from measurements in unbuffered NaClO4 solutions (0.1M) at a starting pH close to neutrality, where 3 and 4 are present in equilibrium. In this case, a fit function describing the pH-time curve allowed the determination of the actual concentrations of 3, 4, and the dihydroxo complex. The platination rate constants characterizing the bimolecular reactions between either I or II and 2, 3, and 4 were individually determined along with the rate constants for hydrolysis of the chloro-monoadducts and for the chelation reactions of the aqua-monoadducts. The reactivity of compounds 2-5, which have the general formula cis-[Pt(NH3)2(H2O)(Y)]2+/-, decreases in the order 3>4>5>>2, that is, Y= H2O > OH- >NH3 >> Cl-, which is the order of decreasing hydrogen-bond donating ability of Y. Deprotonation of 3 to 4 reduces the reactivity of the platinum complex only by a factor of approximately equals 2, and both complexes discriminate between the different purines of I and II in the same manner. Whereas 3 and 4 react approximately three times faster with the GG sequence of I than with the AG sequence of II, 2 shows a similar reactivity towards both sequences. In view of the well-established preferential binding of cisplatin to GG sequences of DNA in vivo and in vitro, this result suggests that the actual DNA platination species are derived from double hydrolysis of cisplatin.

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Platination Pathways for Reactions of Cisplatin with GG Single‐Stranded and Double‐Stranded Decanucleotides

Cited by 58 publications

References 15 publications

Steric Determinants of Pt/DNA Interactions and Anticancer Activity

Steric Determinants of Pt/DNA Interactions and Anticancer Activity

Reactions of the Double‐Stranded Oligonucleotide d(TTGGCCAA)₂withcis‐[Pt(NH₃)₂(H₂O)₂]²⁺and [Pt(NH₃)₃(H₂O)]²⁺

A Complete Kinetic Study of GG versus AG Platination Suggests That the Doubly Aquated Derivatives of Cisplatin Are the Actual DNA Binding Species

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Platination Pathways for Reactions of Cisplatin with GG Single‐Stranded and Double‐Stranded Decanucleotides

Cited by 58 publications

References 15 publications

Steric Determinants of Pt/DNA Interactions and Anticancer Activity

Steric Determinants of Pt/DNA Interactions and Anticancer Activity

Reactions of the Double‐Stranded Oligonucleotide d(TTGGCCAA)2withcis‐[Pt(NH3)2(H2O)2]2+and [Pt(NH3)3(H2O)]2+

A Complete Kinetic Study of GG versus AG Platination Suggests That the Doubly Aquated Derivatives of Cisplatin Are the Actual DNA Binding Species

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Reactions of the Double‐Stranded Oligonucleotide d(TTGGCCAA)₂withcis‐[Pt(NH₃)₂(H₂O)₂]²⁺and [Pt(NH₃)₃(H₂O)]²⁺