ISSN:
0947-6539
Keywords:
antitumor agents
;
DNA
;
kinetics
;
platinum complexes
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The kinetics of the reactions between the GG-containing double-stranded oligonucleotide d(TTGGCCAA)2 (II) and the platinum complexes cis-[Pt-(NH3)2(H2O)2]2+ (1) and [Pt(NH3)3-(H2O)]2+ (2) were studied and compared with those already determined for the reactions of the single-stranded octanucleotide d(CTGGCTCA) (I).[1] The results were as follows: i) Complex 1 reacted faster than 2 with both I and II. ii) Both complexes 1 and 2 reacted faster with II than with I. This acceleration was greater for 1 (x 13) than for 2 (x4) and only due to the increase of the platination rate of the 5′-G of the GG sequence. iii) For both I and II, the first platination by 1 and 2 was faster on the 5′-G than on the 3′-G. This difference was more significant for the platination of II (k5′/k3′ = 12 for 1 and 5 for 2) than of I (k5′/k3′ ≤ 2). iv) The cyclization reaction of the monoadducts (G*) of 1 to yield the GG cis-Pt(NH3)2+2 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* monoaducts (k3′c) was faster than that of the 5′-G* monoadducts (k5′c), both for I and II (k3′c/k5′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′-Gs 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 (k5′ 〈 k3′) and was chelated more slowly (k5′c 〉 k3′i 〈 k3′c), exhibited a half-life of 3.2 h under our experimental conditions.
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chem.1460020904
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