Maeda Rina, Bando Toshikazu, Sugiyama Hiroshi
Graduate School of Advanced Integrated Studies in Human Survivability, Kyoto University, Sakyo-ku, Kyoto, 606-8306, Japan.
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.
Chembiochem. 2021 May 4;22(9):1538-1545. doi: 10.1002/cbic.202000752. Epub 2021 Feb 4.
Pyrrole-imidazole (PI) polyamides, which target specific DNA sequences, have been studied as a class of DNA minor-groove-binding molecules. To investigate the potential of compounds for cancer treatment, PI polyamides were conjugated with DNA-alkylating agents, such as seco-CBI and chlorambucil. DNA-alkylating PI polyamides have attracted attention because of their sequence-specific alkylating activities, which contribute to reducing the severe side effects of current DNA-damaging drugs. Many of these types of conjugates have been developed as new candidates for anticancer drugs. Herein, we review recent progress into research on DNA-alkylating PI polyamides and their sequence-specific action on targets associated with cancer development.
吡咯-咪唑（PI）聚酰胺可靶向特定的DNA序列，作为一类DNA小沟结合分子已得到研究。为了研究化合物用于癌症治疗的潜力，PI聚酰胺与DNA烷基化剂（如司可-喜树碱（seco-CBI）和苯丁酸氮芥）进行了偶联。DNA烷基化PI聚酰胺因其序列特异性烷基化活性而受到关注，这种活性有助于减少当前DNA损伤药物的严重副作用。许多这类偶联物已被开发为抗癌药物的新候选物。在此，我们综述了DNA烷基化PI聚酰胺的研究进展及其对与癌症发展相关靶点的序列特异性作用。
