AMINOGLYCOSIDE/RNA INTERACTIONS AND CORNEAL INFECTIONS
氨基糖苷/RNA 相互作用和角膜感染
基本信息
- 批准号:2739207
- 负责人:
- 金额:$ 25.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-12-01 至 2003-11-30
- 项目状态:已结题
- 来源:
- 关键词:RNA RNA binding protein aminoglycoside antibiotics binding sites chemical binding cornea disorder drug adverse effect drug design /synthesis /production drug interactions eye disorder chemotherapy eye infections gentamicins molecular shape neomycin nuclear magnetic resonance spectroscopy nucleic acid inhibitor nucleic acid structure
项目摘要
RNA molecules are able to form precise three-dimensional structures which can be binding-sites for small organic molecules. An understanding of the rules that govern RNA/small molecule recognition processes rules would allow for an approach to our long-term goal of the de novo design of antagonists directed at particular RNA structures, in much the same way that inhibitors are designed for protein-based enzymes and receptors. Specific inhibitors designed to inhibit RNA molecules could be of enormous interest in ophthalmology and generally in medicine, in the design, for example, of small-molecules that can specifically interfere with the expression of mutant proteins that can lead to retinal degeneration, and in the design of small molecules that can antagonize RNA molecules from infectious disease producing organisms. This proposal describes approaches to gaining an understanding of the rules by which certain classes of naturally occurring RNA antagonists, the aminoglycosides, are recognized by specific RNA molecules. Random RNA molecules are selected by column methods to bind to defined aminoglycoside containing antibiotics with high affinity and specificity. New quantitative fluorescence methods are developed to determine the affinities and stoichiometries of antibiotic binding to the selected RNA aptamers. Novel chemical approaches are developed to reveal the regions of the aptamers which define the binding-sites for the specific antibiotic. High field NMR structural studies on the high affinity binding aptamers are planned. Those motifs in the specific RNA aptamers which recognize particular aminoglycosides will be determined and used as a guide for the future design of specific antagonists directed against naturally occurring RNA molecules. Two biologically occurring RNA molecules of particular interest in this context are the procaryotic 16S rRNA decoding region and the HIV-RRE transcriptional activator region. Quantitative structure-activity studies on aminoglycoside binding to the decoding and RRE regions leads to the design of novel aminoglycosidemimetic diversity libraries containing l,3(2)-hydroxylamine moieties. Specific antagonists directed against the decoding and RRE regions of RNA will be prepared and studies quantitatively. These antagonists are expected to be starting points for the design of drugs useful in the treatment of corneal infections. Overall, the studies described herein will serve as the basis for a general program on the design of specific RNA antagonists.
RNA分子能够形成精确的三维结构,这些结构可以作为有机小分子的结合位点。 了解RNA/小分子识别过程的规则,将有助于我们实现长期目标,即针对特定RNA结构重新设计拮抗剂,就像针对蛋白质酶和受体设计抑制剂一样。 设计用于抑制RNA分子的特异性抑制剂在眼科学和一般医学中,例如在设计可特异性干扰可导致视网膜变性的突变蛋白质的表达的小分子中,以及在设计可拮抗来自产生传染病的生物体的RNA分子的小分子中,可能引起极大的兴趣。该提案描述了获得对某些类别的天然存在的RNA拮抗剂(氨基糖苷类)被特定RNA分子识别的规则的理解的方法。 通过柱方法选择随机RNA分子,以高亲和力和特异性结合限定的含有氨基糖苷类的抗生素。 开发了新的定量荧光方法来确定抗生素与所选RNA适体结合的亲和力和化学计量。 开发了新的化学方法来揭示定义特定抗生素结合位点的适体区域。 计划对高亲和力结合适体进行高场NMR结构研究。 将确定识别特定氨基糖苷类的特异性RNA适体中的那些基序,并将其用作针对天然存在的RNA分子的特异性拮抗剂的未来设计的指导。在这种情况下,特别感兴趣的两种生物学上存在的RNA分子是原核16 S rRNA解码区和HIV-RRE转录激活因子区。 对氨基糖苷类化合物结合到解码区和RRE区的定量结构-活性研究导致了含有1,3(2)-羟胺部分的新型氨基糖苷类化合物多样性文库的设计。 针对RNA的解码和RRE区域的特异性拮抗剂将被制备和定量研究。这些拮抗剂有望成为设计用于治疗角膜感染的药物的起点。 总之,本文所述的研究将作为设计特异性RNA拮抗剂的一般程序的基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
ROBERT R RANDO其他文献
ROBERT R RANDO的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('ROBERT R RANDO', 18)}}的其他基金
Retinyl Ester Binding Proteins and the Visual Cycle
视黄酯结合蛋白和视觉周期
- 批准号:
7001202 - 财政年份:2005
- 资助金额:
$ 25.59万 - 项目类别:
Retinyl Ester Binding Proteins and the Visual Cycle
视黄酯结合蛋白和视觉周期
- 批准号:
6855567 - 财政年份:2005
- 资助金额:
$ 25.59万 - 项目类别:
Retinyl Ester Binding Proteins and the Visual Cycle
视黄酯结合蛋白和视觉周期
- 批准号:
7176097 - 财政年份:2005
- 资助金额:
$ 25.59万 - 项目类别:
AMINOGLYCOSIDE/RNA INTERACTIONS AND CORNEAL INFECTIONS
氨基糖苷/RNA 相互作用和角膜感染
- 批准号:
6476401 - 财政年份:1998
- 资助金额:
$ 25.59万 - 项目类别:
AMINOGLYCOSIDE/RNA INTERACTIONS AND CORNEAL INFECTIONS
氨基糖苷/RNA 相互作用和角膜感染
- 批准号:
6625011 - 财政年份:1998
- 资助金额:
$ 25.59万 - 项目类别:
AMINOGLYCOSIDE/RNA INTERACTIONS AND CORNEAL INFECTIONS
氨基糖苷/RNA 相互作用和角膜感染
- 批准号:
6329574 - 财政年份:1998
- 资助金额:
$ 25.59万 - 项目类别:
AMINOGLYCOSIDE/RNA INTERACTIONS AND CORNEAL INFECTIONS
氨基糖苷/RNA 相互作用和角膜感染
- 批准号:
6125153 - 财政年份:1998
- 资助金额:
$ 25.59万 - 项目类别:
MEDICINAL CHEMISTRY OF NOVEL ANTITHROMBOTIC DRUGS
新型抗血栓药物的药物化学
- 批准号:
3347148 - 财政年份:1985
- 资助金额:
$ 25.59万 - 项目类别:
MEDICINAL CHEMISTRY OF NOVEL ANTITHROMBOTIC DRUGS
新型抗血栓药物的药物化学
- 批准号:
3347146 - 财政年份:1985
- 资助金额:
$ 25.59万 - 项目类别:
MEDICINAL CHEMISTRY OF NOVEL ANTITHROMBOTIC DRUGS
新型抗血栓药物的药物化学
- 批准号:
3347153 - 财政年份:1985
- 资助金额:
$ 25.59万 - 项目类别:
相似海外基金
Role of novel RNA binding protein LARP6 in alcoholic cardiomyopathy
新型RNA结合蛋白LARP6在酒精性心肌病中的作用
- 批准号:
10593688 - 财政年份:2023
- 资助金额:
$ 25.59万 - 项目类别:
Targeting of RNA-binding protein FXR1 in HNSCC
HNSCC 中 RNA 结合蛋白 FXR1 的靶向
- 批准号:
10571379 - 财政年份:2023
- 资助金额:
$ 25.59万 - 项目类别:
Mechanisms driving Autosomal Dominant Polycystic Kidney Disease: The novel role of the RNA-binding protein ANKHD1.
常染色体显性多囊肾病的驱动机制:RNA 结合蛋白 ANKHD1 的新作用。
- 批准号:
MR/T04201X/2 - 财政年份:2023
- 资助金额:
$ 25.59万 - 项目类别:
Fellowship
Identify the role of RNA-binding protein in activating anti-tumor immunity by directly decaying PD-L1-3'UTR
通过直接降解 PD-L1-3UTR 鉴定 RNA 结合蛋白在激活抗肿瘤免疫中的作用
- 批准号:
23KJ1296 - 财政年份:2023
- 资助金额:
$ 25.59万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Anti-inflammatory Signaling of RNA-binding Protein, Tristetraprolin, During Myocardial Infarction
RNA 结合蛋白 Tristetraprolin 在心肌梗死期间的抗炎信号传导
- 批准号:
10644962 - 财政年份:2023
- 资助金额:
$ 25.59万 - 项目类别:
Formation and function of pathologic stress granules containing RNA-Binding Protein SFPQ in tauopathy
tau蛋白病中含有RNA结合蛋白SFPQ的病理应激颗粒的形成和功能
- 批准号:
10581946 - 财政年份:2023
- 资助金额:
$ 25.59万 - 项目类别:
ERK-mediated regulation of RNA binding protein condensation during female germ cell development
ERK 介导的雌性生殖细胞发育过程中 RNA 结合蛋白凝聚的调节
- 批准号:
10514951 - 财政年份:2022
- 资助金额:
$ 25.59万 - 项目类别:
Role of RNA-binding protein in immune evasion of Mtb in macrophages
RNA结合蛋白在巨噬细胞中Mtb免疫逃避中的作用
- 批准号:
10634764 - 财政年份:2022
- 资助金额:
$ 25.59万 - 项目类别:
Post-transcriptional regulation by the YBX3 RNA-binding protein in skeletal muscle
骨骼肌中 YBX3 RNA 结合蛋白的转录后调节
- 批准号:
10439013 - 财政年份:2022
- 资助金额:
$ 25.59万 - 项目类别:
Evolution of RNA Binding Protein Regulation of Brain Development
RNA结合蛋白对大脑发育调节的进化
- 批准号:
2735241 - 财政年份:2022
- 资助金额:
$ 25.59万 - 项目类别:
Studentship