Synthesis and Chemical Biology of Thiopeptide Antibiotics
硫肽类抗生素的合成及化学生物学
基本信息
- 批准号:10581377
- 负责人:
- 金额:$ 19.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AntibioticsAzolesBiologyChemicalsClinical ResearchDevelopmentDiseaseESKAPE pathogensElementsHealthHealthcare SystemsHumanLightMethodsMicrobiologyModificationMutationPeptidesPreparationSiteTreatment Protocolsantimicrobialantimicrobial drugantimicrobial peptideantimicrobial resistant pathogenbioactive natural productsbiophysical analysisclinical investigationcomputer studiesdesigneconomic costinnovationnovel therapeuticspre-clinicalpreclinical studypredictive modelingresistant strainstandard caretooltranslational potential
项目摘要
PROJECT SUMMARY/ABSTRACT
Antibiotics have transformed the human health and disease landscape. However, the use and
misuse of such antimicrobial drugs accelerate the emergence of bacterial strains resistant
against antibiotics, so that standard treatment options eventually become ineffective. In light of
these critical needs, thiopeptides have emerged as a promising platform for the discovery of
new therapeutic leads. In Aim 1, we will develop and optimize the preparation of 26-membered
thiopeptides by inventing a new cyclodehydration methods to facilitate the synthetic campaign.
The methods established in this aim will be validated in the context of representative
azole/azoline-containing antimicrobial peptides. In Aim 2, we will optimize a streamlined
synthesis of 35-membered thiopeptides by integrating Mo-catalyzed cyclodehydrations and site-
selective Dha mutations. These findings will unlock the translational potential of a previously
unexplored class of potent antibiotics. In Aim 3, we will develop an automated platform for
rational thiopeptide design and modifications, and integrate it with microbiological, biophysical,
and computational studies to generate promising leads suitable for pre-clinical and clinical
investigations. Successful realization of the abovementioned aims will establish innovative tools
for the synthesis of thiopeptides and other bioactive macrocyclic peptides. Because of the
importance of azol(in)es as the key structural elements in bioactive natural products of
biomedical relevance, the discoveries of this study will have a transformative impact on the
development of new therapies.
项目总结/文摘
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(0)
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Maciej Walczak其他文献
Maciej Walczak的其他文献
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{{ truncateString('Maciej Walczak', 18)}}的其他基金
Dissecting the role of tau glycosylation in Alzheimer's disease
剖析 tau 糖基化在阿尔茨海默病中的作用
- 批准号:
10662150 - 财政年份:2023
- 资助金额:
$ 19.43万 - 项目类别:
Synthesis and Chemical Biology of Thiopeptide Antibiotics
硫肽类抗生素的合成及化学生物学
- 批准号:
10557848 - 财政年份:2021
- 资助金额:
$ 19.43万 - 项目类别:
Synthesis and Chemical Biology of Thiopeptide Antibiotics
硫肽类抗生素的合成及化学生物学
- 批准号:
10373087 - 财政年份:2021
- 资助金额:
$ 19.43万 - 项目类别:
Synthesis and Chemical Biology of Thiopeptide Antibiotics
硫肽类抗生素的合成及化学生物学
- 批准号:
10211882 - 财政年份:2021
- 资助金额:
$ 19.43万 - 项目类别:
New Catalytic Methods for the Synthesis of Biomedically Relevant Carbohydrates
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- 批准号:
9391514 - 财政年份:2017
- 资助金额:
$ 19.43万 - 项目类别:
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