CRYSTALLOGRAPHIC STUDIES OF NOVEL PROTEIN SYNTHESIS

新型蛋白质合成的晶体学研究

• 批准号: 7957249
• 负责人: Joseph Ippolito
• 金额: $ 1.75万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957249
• 关键词: Address; Affinity; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics; Binding; Chemicals; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Funding; Goals; Grant; Haloarcula marismortui; Housing; Institution; Light; Pharmaceutical Preparations; Pharmacologic Substance; Process; Protein Biosynthesis; Research; Research Personnel; Resolution; Resources; Ribosomes; Source; Staging; Structure; Synchrotrons; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 Rib-X Pharmaceuticals，Inc。是一家早期的制药公司，其陈述的目标是通过发现针对核糖体的抗抗形态的新型化学化学类别类别，以提高对当前抗菌剂的细菌耐药性来解决所带来的困难。 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，该策略利用了与小分子抑制剂复合的Haloarcula marismortui的50S核糖体的高分辨率晶体结构。 这些分子的范围从已知的抗生素铅到基于我们先前的结构结果设计和合成的化合物。 由此产生的结构信息将作为进一步的化合物设计的指南，旨在提高结合亲和力并提高类似药物的整体品质。