CRYSTALLOGRAPHIC STUDIES OF NOVEL PROTEIN SYNTHESIS

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。RIB-X制药公司是一家初创阶段的制药公司，其宣称的目标是通过发现针对核糖体的新型抗感染药物来解决细菌对当前抗菌剂的抗药性增加带来的困难。为了缩短药物发现过程，我们采用了一种基于结构的设计策略，利用海洋盐藻50S核糖体的高分辨率晶体结构与小分子抑制剂复合。这些分子的范围从已知的抗生素先导到根据我们之前的结构结果自行设计和合成的化合物。由此得到的结构信息将作为进一步化合物设计的指南，旨在增加结合亲和力和改善整体类药物质量。

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. Rib-X Pharmaceuticals, Inc. is an early stage pharmaceutical company whose stated goal is to address the difficulties presented by increasing bacterial resistance against current antibacterial agents by discovering novel chemical classes of anti-infectives that target the ribosome. In order to shorten the drug discovery process, we are employing a structure-based design strategy utilizing high resolution crystal structures of the 50S ribosome from Haloarcula marismortui complexed with small molecule inhibitors. These molecules range from known antibiotic leads, to compounds designed and synthesized in-house based on our previous structural results. The resulting structural information will serve as a guide for further compound designs that aim to increase binding affinity and improve overall drug-like qualities.