Reactions of the double-stranded oligonucleotide d(TTGGCCAA)(2) with cis-[Pt(NH3)(2)(H2O)(2)](2+) and [Pt(NH3)(3)(H2O)](2+)

The kinetics of the reactions between the GG-containing double-stranded oligonucleotide d(TTGGCCAA)(2) (TI) 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 re; actions 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-Il. ii) Both complexes 1 and 2 reacted faster with II than with I. This acceleration was greater for 1 (x13) 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 (k(5)'/k(3)'=12 for 1 and 5 for 2) than of I (k(5)'/k(3)'less than or equal to 12), iv) The cyclization reaction of the monoadducts (G*) of 1 to yield the GC 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* monoadducts (k(3'c)) was faster than that of the 5'-G* monoadducts (k(5'c)), both for I and II (k(3'c)/k(5'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 (k(3'i)) was half that of the intrastrand chelation (k(3'c)). vii) The 5' monoadduct, which was formed faster (k(5')>k(3')) and was chelated more slowly (k(5'c)much less than K-3'i<k(3'c)), exhibited a half-life of 3.2 h under our experimental conditions.