Reactions of the Double‐Stranded Oligonucleotide d(TTGGCCAA)₂ with <i>cis</i>‐[Pt(NH₃)₂(H₂O)₂]²⁺ and [Pt(NH₃)₃(H₂O)]²⁺

Abstract

Abstract The kinetics of the reactions between the GG‐containing double‐stranded oligonucleotide d(TTGGCCAA) 2 ( II ) and the platinum complexes cis ‐[Pt‐(NH 3 ) 2 (H 2 O) 2 ] 2+ ( 1 ) and [Pt(NH 3 ) 3 ‐(H 2 O)] 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 ( k 5′ / k 3′ = 12 for 1 and 5 for 2 ) than of I ( k 5′ / k 3′ ≤ 2). iv) The cyclization reaction of the monoadducts (G * ) of 1 to yield the GG cis ‐Pt(NH 3 ) 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′ &lt; k 3′ ) and was chelated more slowly ( k 5′c &gt; k 3′i &lt; k 3′c ), exhibited a half‐life of 3.2 h under our experimental conditions.