Baruah Hemanta, Day Cynthia S, Wright Marcus W, Bierbach Ulrich
Department of Chemistry, Wake Forest University, P.O. Box 7486, Reynolda Station, Winston-Salem, North Carolina 27109, USA.
J Am Chem Soc. 2004 Apr 14;126(14):4492-3. doi: 10.1021/ja038592j.
The crystal structure of the excised major DNA monoadduct, [Pt(en)(ACRAMTU-S)(dGuo-N7)]3+ ("dGuo*"; en = ethane-1,2-diamine; ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea, acridinium cation; dGuo = 2'-deoxyguanosine), of a platinum-acridine cytotoxic agent is reported. The adduct dGuo*, previously identified in enzymatic digests of native DNA treated with this drug, is partially deprotonated and dimerizes through formation of a rare GG- mismatch base pair, which is sandwiched between the planar chromophores of the acridine nonleaving groups linked to platinum. NMR evidence exists that indicates that the dimeric form persists in neutral aqueous solution. The one-dimensional pi-stack produced by the dimers in the solid state is reminiscent of a coordinative-intercalative DNA binding mode.
报道了一种铂 - 吖啶细胞毒性剂切除的主要DNA单加合物[Pt(en)(ACRAMTU - S)(dGuo - N7)]3 +（“dGuo*”；en = 乙二胺；ACRAMTU = 1 - [2 - (吖啶 - 9 - 基氨基)乙基] - 1,3 - 二甲基硫脲，吖啶鎓阳离子；dGuo = 2'-脱氧鸟苷）的晶体结构。加合物dGuo*先前在经该药物处理的天然DNA的酶消化物中被鉴定出来，它部分去质子化，并通过形成罕见的GG错配碱基对二聚化，该碱基对夹在与铂相连的吖啶非离去基团的平面发色团之间。有核磁共振证据表明二聚体形式在中性水溶液中持续存在。固态中二聚体产生的一维π堆积让人联想到配位 - 插入式DNA结合模式。
