CRYSTALLOGRAPHIC STUDIES OF NOVEL PROTEIN SYNTHESIS

新型蛋白质合成的晶体学研究

• 批准号: 7726260
• 负责人: Joseph Ippolito
• 金额: $ 1.1万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-18 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726260
• 关键词: Address; Affinity; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics; Binding; Chemicals; Class; Complex; Computer Retrieval of Information on Scientific Projects Database; Funding; Goals; Grant; Haloarcula marismortui; Housing; Institution; Pharmaceutical Preparations; Pharmacologic Substance; Process; Protein Biosynthesis; Range; Research; Research Personnel; Resolution; Resources; Ribosomes; Source; Staging; Structure; United States National Institutes of Health; bacterial resistance; base; design; drug discovery; improved; inhibitor/antagonist; novel; rib bone structure; small molecule

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 Rib-X Pharmaceuticals，Inc.是一家早期的制药公司，其既定目标是通过发现新的化学类别的抗感染药物来解决增加细菌对当前抗菌剂的耐药性所带来的困难， 核糖体 为了缩短药物发现过程，我们采用了基于结构的设计策略，利用来自Haloarcula marismortui的50 S核糖体与小分子抑制剂复合的高分辨率晶体结构。 这些分子的范围从已知的抗生素先导化合物到基于我们以前的结构结果内部设计和合成的化合物。 所得到的结构信息将作为进一步化合物设计的指导，旨在增加结合亲和力和改善整体药物样质量。