Design of DNA-cleaving and -crosslinking agents based on NFκB and HMGA proteins aiming at the application to cancer therapy

近年来，核因子κB和hMGA蛋白因与肿瘤的发生和侵袭有关而备受关注。本研究旨在设计和合成基于核因子κB和HMGA蛋白的DNA裂解/交联分子。这种配体形成亚铁络合物，产生氧自由基，裂解DNA。在本研究中，我们成功地制备了一种新的基于二甲氨基吡啶/组氨酸的配体，该配体配备了一个氯烷基连接物，可以原位结合各种蛋白质的SH基团。这将使我们能够切割NFκB和HMGA蛋白识别的dna序列。

Recently, NFκB and HMGA proteins attract the interest because of their relation to carcinogenesis and tumor invasion. The present study aimed at design and synthesis of DNA-cleaving/crosslinking molecules based on the NFκB and HMGA proteins.We first synthesized a novel artificial ligand comprising a dimethylaminopyridine and histidines. This ligand formed ferrous complex to generate oxygen radical, cleaving DNA. In the present study, we are successful to prepare a new dimethylaminopyridine/histidine based ligand equipped with a chloroalkyl linker that could bind a SH group of various proteins in situ. This would enable us to cleave DNA sequences that NFκB and HMGA proteins recognize.