Dalbiès R, Payet D, Leng M
Centre de Biophysique Moléculaire, Centre National de la Recherche Scientifique, Orleans, France.
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8147-51. doi: 10.1073/pnas.91.17.8147.
In the reaction between trans-diamminedichloroplatinum(II) and a single-stranded pyrimidin-rich oligodeoxyribonucleotide (22-mer) containing the central sequence TGAGT, the 1,3-trans-[Pt(NH3)2[d(GAG)]] cross-link is formed. The 1,3-intrastrand cross-link is inert within the single-stranded oligonucleotide. In contrast, it rearranges to an interstrand cross-link when the platinated oligonucleotide is paired with its complementary deoxyribo- or ribonucleotide strand. The half-life of the 1,3-intrastrand cross-link, approximately 6 h at 37 degrees C, is independent of the nature and concentration of the salt (NaCl or NaClO4). It is not dramatically affected when the intervening adenine residue between the chelated guanine residues is replaced by a cytosine or a thymine residue or when the T.A base pair adjacent to the 5' or 3' side of the adduct is replaced by a C.G base pair. On the other hand, a mismatch on the 3' or 5' side of the adduct prevents the rearrangement. We propose that the linkage isomerization reaction results from a direct nucleophilic attack of the cytosine residue complementary to the platinated 5' guanine residue on the platinum residue. Among others, the potential use of the DNA.RNA-promoted reaction is discussed in the context of the antisense strategy to irreversibly cross-link the antisense oligonucleotides to their targets.
在反式二氯二氨合铂（II）与含有中心序列TGAGT的富含嘧啶的单链寡聚脱氧核糖核苷酸（22聚体）之间的反应中，形成了1,3 - 反式 - [Pt(NH₃)₂[d(GAG)]]交联。这种1,3 - 链内交联在单链寡核苷酸内是惰性的。相反，当铂化的寡核苷酸与其互补的脱氧核糖或核糖核苷酸链配对时，它会重排为链间交联。1,3 - 链内交联的半衰期在37℃时约为6小时，与盐（NaCl或NaClO₄）的性质和浓度无关。当螯合的鸟嘌呤残基之间的中间腺嘌呤残基被胞嘧啶或胸腺嘧啶残基取代，或者加合物5'或3'侧相邻的T.A碱基对被C.G碱基对取代时，它不会受到显著影响。另一方面，加合物3'或5'侧的错配会阻止重排。我们提出，连接异构化反应是由与铂化的5'鸟嘌呤残基互补的胞嘧啶残基对铂残基的直接亲核攻击引起的。此外，还在反义策略的背景下讨论了DNA.RNA促进反应将反义寡核苷酸与其靶标不可逆交联的潜在用途。
