Studies towards peptide and protein chemical synthesis using strained thiolactones

使用应变硫内酯进行肽和蛋白质化学合成的研究

基本信息

批准号：
1710174
负责人：
Qiang Zhang
金额：
$ 37.5万
依托单位：
SUNY at Albany
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1710174&HistoricalAwards=false
关键词：
Studies towards peptide protein chemical

项目摘要

The Chemical Synthesis Program of the Chemistry Division supports the project of Professor Qiang Zhang in the Department of Chemistry at the State University of New York at Albany. He is developing state-of-the-art methods for building peptide and protein connections. The goal of Professor Zhang's research is to establish efficient and practical approaches to synthesize polypeptides, proteins, and glycoproteins through utilization of strained molecules. The work is of major importance because scientists in a broad range of fields require these biological polymers to study cellular processes in plants, animals, and humans. The project's goals are to enable scientists to efficiently prepare biomacromolecules that can be utilized to make advancements in diverse fields including molecular biology, cellular biochemistry, agriculture, pharmaceutical synthesis, medicine, and in the development of treatments for numerous diseases. Professor Zhang's research integrates the disciplines of organic synthesis, carbohydrate modification, and glycobiology in a manner that provides unique educational opportunities for women and other students historically underrepresented in science, technology, engineering and mathematics. Currently, there are a variety of synthetic methods in chemistry, including solid-phase peptide synthesis, native chemical ligation, and metal-free dethionylation that have been developed for obtaining polypeptides and proteins. However, conventional methods for their synthesis have a number of disadvantages that limit the diversity of peptides and proteins that can be produced and the quantities that can be made. Additional challenges include the number of reaction steps required, and the need for time-consuming post-synthesis purifications after each step. By taking advantage of the strain of beta-thiolactone and its derivatives, the researchers are developing a protocol for thioester-free peptide ligation. Furthermore, the facile reactivity of beta-thiolactones enable multi-component one-pot native chemical ligation and metal-free dethionylation procedures to synthesize complex proteins and glycoproteins. The realization of this approach establishes an efficient route for the chemical synthesis of biologics with minimal separation efforts and maximum reaction output. In addition, the installation of different carbohydrate building blocks into the peptidyl backbone generates homogeneous glycoproteins with different glycoforms; they can be employed for in-depth evaluation of complex glycoproteins that are important in biological systems. The integrated education and research training is preparing a diverse group of project trainees for rewarding careers, and greatly enhance their readiness and competitiveness for employment opportunities in a broad range of scientific fields.

化学部的化学合成计划支持纽约州立大学奥尔巴尼大学化学系教授的项目。他正在开发建立肽和蛋白质连接的最新方法。张教授的研究的目的是建立有效且实用的方法，通过利用紧张的分子来合成多肽，蛋白质和糖蛋白。这项工作至关重要，因为广泛领域的科学家要求这些生物聚合物研究植物，动物和人类的细胞过程。该项目的目标是使科学家能够有效地准备可用于在包括分子生物学，细胞生物化学，农业，药物合成，医学以及多种疾病的治疗发展的不同领域的进步。张教授的研究将有机综合，碳水化合物修饰和糖生物学的学科融合为为妇女和其他学生提供独特的教育机会，历史上在科学，技术，工程和数学方面具有不足的代表性。当前，化学中有多种合成方法，包括用于获得多肽和蛋白质的固相肽合成，天然化学连接和无金属二硫代化。但是，其合成的常规方法具有许多缺点，这些缺点限制了可以生产的肽和蛋白质的多样性以及可以制造的数量。其他挑战包括所需的反应步骤的数量，以及每一步之后对耗时的耗时的合成后净化的需求。通过利用β-硫代酮及其衍生物的菌株，研究人员正在开发无硫酯的肽结扎方案。此外，β-硫代酮的便利反应性使多组分的一锅天然化学连接和无金属的脱硫程序能够合成复杂的蛋白质和糖蛋白。这种方法的实现为生物制剂化学合成的有效途径以最小的分离工作和最大的反应输出而建立了有效的途径。此外，将不同的碳水化合物构建块安装到肽基骨架中会产生具有不同糖型的均质糖蛋白。它们可以用于对生物系统重要的复杂糖蛋白进行深入评估。综合的教育和研究培训正在为各种各样的项目受训者做准备，以奖励职业，并在广泛的科学领域中大大提高了他们的就业机会的准备和竞争力。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Convergent Palladium-Catalyzed Stereospecific Arginine Glycosylation Using Glycals.

DOI：
10.1021/acs.orglett.1c01218
发表时间：
2021-05-21
期刊：
Organic letters
影响因子：
5.2
作者：
Yang J;Dai Y;Bartlett R;Zhang Q
通讯作者：
Zhang Q

Three-Component Protein Modification Using Mercaptobenzaldehyde Derivatives

DOI：
10.1021/acs.orglett.9b01294
发表时间：
2019-05-17
期刊：
ORGANIC LETTERS
影响因子：
5.2
作者：
Dai, Yuanwei;Weng, Jiaping;Zhang, Qiang
通讯作者：
Zhang, Qiang

Oxidative phenol-arene and phenol-phenol cross-coupling using periodic acid

DOI：
10.1016/j.tet.2019.02.021
发表时间：
2019-03-29
期刊：
TETRAHEDRON
影响因子：
2.1
作者：
Gao, Peng-Cheng;Chen, Huan;Zhang, Qiang
通讯作者：
Zhang, Qiang

Radical functionalization of thioglycosides in aqueous medium

水介质中硫代糖苷的自由基官能化

DOI：
10.1016/j.tetlet.2021.153499
发表时间：
2021
期刊：
Tetrahedron Letters
影响因子：
1.8
作者：
Kaur, Sarbjeet;Luciano, Dominic P.;Fan, Xinhao;Zhao, Gaoyuan;Messier, Sheridan;Walker, Madison M.;Zhang, Qiang;Wang, Ting
通讯作者：
Wang, Ting