STRUCTURE BASED DESIGN OF ANTI-INFECTIVE DRUGS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。随着抗药性细菌和病毒疾病成为日益严重的世界卫生问题，迫切需要发现和开发新的抗感染药物。细菌核糖体是氨基糖苷类抗生素的主要靶点，旨在对抗细菌感染。例如，巴洛霉素和妥布霉素等抗生素与16S核糖体亚基内的RNA氨酰解码位点(A位点)结合，通过在蛋白质合成过程中诱导错误编码来干扰翻译，进而导致细菌细胞死亡。A位RNA和其他细菌核糖体RNA药物靶标的详细高分辨率晶体结构将有助于阐明RNA靶标与这些抗生素之间的相互作用，并将有助于基于结构的新型抗生素的设计。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The discovery and development of new anti-infective drugs is urgently needed, as drug-resistant bacterial and viral diseases become an increasingly serious world health problem. The bacterial ribosome is a primary target of aminoglycoside antibiotics designed to combat bacterial infection. For instance, antibiotics such as paromomycin and tobramycin bind to the RNA aminoacyl decoding site (A-site) within the 16S ribosomal subunit and interfere with translation by inducing miscoding during the protein synthesis, which in turn leads to the death of the bacterial cell. The detailed high-resolution crystal structures of the A-site RNA and other bacterial ribosomal RNA drug targets will allow the elucidation of the interactions between the RNA target and these antibiotics, and will facilitate the structure-based design of novel antibiotics.