Preparation of Artificial Ribonucleases and Their Applications to the Therapy for Cancer and AIDS

点击翻译按钮获取中文摘要

With the aims to develop new therapeutic methods for cancer and AIDS,artificial ribonucleases have been prepared, and RNA scission mechanism is investigated. It is confirmed that intramolecular acid/base cooperation is responsible for the remarkable catalysis of oligoamines for RNA hydrolysis. Novel artificial ribonucleases in which oligoamines are attached inside of DNA oligomers (which are complementary with a part of the substrate RNA) have been synthesized. These artificial enzymes cut the target RNA more precisely than the ones with the scissors at the ends of DNA oligomers, mainly because the scissors are fixed in the rigidly structured double strands. Furthermore, Conjugates of an intercalator and either glycine or iminodiacetate show effective scission of RNA.These conjugates are neutral or negatively charged, which is highly in contrast with the fact that the previously reported RNA scissors are positively charged. Thus, they can be placed exactly at the desired site, even in a strong electrostatic field induced by RNA.These artificial ribonucleases cleave only the target RNA in cells, and thus should be highly potent for the therapy of cancer and AIDS.