RNA: New Antimicrobial Strategies

RNA：新的抗菌策略

• 批准号: 8939899
• 负责人: Adrian Ferre-D'Amare
• 金额: $ 70.5万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8939899
• 关键词: Adopted; Affinity; Agonist; Alternative Splicing; Antibiotic Resistance; Antibiotics; Bacillus (bacterium); Binding; Biochemical; Catalytic RNA; Clostridium; Complex; Development; Evolution; Genetic Transcription; Genus staphylococcus; Laboratories; Lead; Ligand Binding; Ligands; Listeria; Location; Metabolic Pathway; Methodology; Molecular; Public Health; Publications; RNA; Regulator Genes; Research; Roentgen Rays; Signal Pathway; Solutions; Specificity; Streptococcus; Structure; Study Subject; Translations; Work; antimicrobial; base; design; functional group; insight; interest; mRNA Decay; novel; novel therapeutics; pathogenic bacteria; response; screening; three dimensional structure; tool

In the past year, two lines of research yielded publications. First, we continue to develop methodology for screening new agonists, antagonists and allosteric effectors of biologically important RNAs. The continued development of solution methodology that can readily detect the molecular response of RNAs to ligand binding, such as small-angle X-ray screening remains a priority. The TPP riboswitch is widely distributed phylogenetically. Previously, our collaborator Dr. Abell and coworkers have carried out a fragment-based screen against this riboswitch and found a number of small organic molecules that bind with high specificity, albeit low affinity, to the RNA. Fragment-based screening is predicated on being able to elucidate the binding location of the low affinity fragments so that they can be elaborated into high affinity binders. Crystallographic work in our laboratory has confirmed the specificity of binding of a number of fragments, and elaboration of these into more potent ligands for the TPP riboswitch is underway.

在过去的一年中，两条研究产生了出版物。 首先，我们继续开发筛查生物学上重要RNA的新激动剂，拮抗剂和变构效应的方法。 溶液方法的持续开发可以容易地检测RNA对配体结合的分子反应，例如小角度X射线筛选仍然是优先的。 TPP核糖开关在系统发育上广泛分布。 以前，我们的合作者Abell博士和同事对这种核糖开关进行了基于碎片的屏幕，并发现许多小的有机分子与RNA具有很高的特异性（尽管低亲和力）结合。 基于片段的筛选是基于能够阐明低亲和力片段的结合位置，从而可以将其详细阐述为高亲和力粘合剂。 我们实验室中的晶体学工作证实了许多片段结合的特异性，并将其阐述为TPP核糖开关的更有效的配体。