DEVELOPMENT OF ANTI-INFECTIVE AGENTS-NATURAL PRODUCT CORE BASED LIBRARY APPROACH

基于天然产物核心的库方法的抗感染剂的开发

• 批准号: 8360698
• 负责人: Dianqing Sun
• 金额: $ 6.89万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360698
• 关键词: Anabolism; Anti-Infective Agents; Antimalarials; Antitubercular Agents; Biological Factors; Cell Wall; Development; Disease; Education; Funding; Goals; Grant; Hawaii; Lead; Libraries; National Center for Research Resources; Nucleosides; Peptides; Principal Investigator; Research; Research Infrastructure; Resources; Screening procedure; Source; United States National Institutes of Health; analog; base; cost; design; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The aim of this proposal is to discover and develop novel anti-infective agents utilizing a natural product core-based library approach. Historically, natural products are known as a rich source of compounds found to be bioactive against a wide range of disease states, in particular as anti-infective drugs or as lead compounds. Specific Aim 1. Further optimization and development of nucleoside peptide anti-tuberculosis agents. We would like to develop nucleoside peptide mimics as novel anti-tuberculosis agents targeting cell wall biosynthesis. To achieve this goal, we aim to design and synthesize a small focused optimization library based on the hits from our primary screens of a nucleoside peptide discovery library that has great structural similarity to the Mureidomycins. Specific Aim 2. Design and synthesis of Gallinamide A analogs as potential antimalarial agents. The purpose of this aim is to develop a feasible synthesis that allows rapid access to Gallinamide A analogs for antimalarial screening. To achieve this goal, we will again use a library core based approach to design and synthesize a diversity oriented library based on a Gallinamide A template.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该提案的目的是利用基于天然产物核心库的方法发现和开发新型抗感染剂。历史上，天然产物被认为是对广泛的疾病状态具有生物活性的化合物的丰富来源，特别是作为抗感染药物或作为先导化合物。 具体目标1。核苷肽类抗结核药物的进一步优化与开发。我们希望开发核苷肽模拟物作为靶向细胞壁生物合成的新型抗结核药物。为了实现这一目标，我们的目标是设计和合成一个小的集中优化库的基础上，从我们的初步筛选的核苷肽发现库，具有很大的结构相似性的Mureidomycins的命中。 具体目标2。作为潜在抗疟剂的Gallinamide A类似物的设计和合成。该目标的目的是开发一种可行的合成，其允许快速获得用于抗疟筛选的Gallinamide A类似物。为了实现这一目标，我们将再次使用基于文库核心的方法来设计和合成基于Gallinamide A模板的多样性导向文库。