Department of Chemistry, Imperial College London, London, SW7 2AZ, UK.
Angew Chem Int Ed Engl. 2018 Jan 2;57(1):310-313. doi: 10.1002/anie.201709968. Epub 2017 Dec 7.
There has been increasing interest in the development of small molecules that can selectively bind to G-quadruplex DNA structures. The latter have been associated with a number of key biological processes and therefore are proposed to be potential targets for drug development. Herein, we report the first example of a reduction-activated G-quadruplex DNA binder. We show that a new octahedral platinum(IV)-salphen complex does not interact with DNA in aqueous media at pH 7.4; however, upon addition of bioreductants such as ascorbic acid or glutathione, the compound is readily reduced to the corresponding square planar platinum(II) complex. In contrast to the parent platinum(IV) complex, the in situ generated platinum(II) complex has good affinity for G-quadruplex DNA.
人们对开发能够选择性结合 G-四链体 DNA 结构的小分子越来越感兴趣。后者与许多关键的生物学过程有关，因此被认为是药物开发的潜在靶点。本文报道了首例还原激活的 G-四链体 DNA 结合物。我们表明，一种新型八面体铂（IV）-席夫碱配合物在 pH 值为 7.4 的水性介质中不与 DNA 相互作用；然而，当加入生物还原剂，如抗坏血酸或谷胱甘肽时，该化合物很容易被还原为相应的平面正方形铂（II）配合物。与母体铂（IV）配合物相比，原位生成的铂（II）配合物对 G-四链体 DNA 具有良好的亲和力。
