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

• 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

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.

化学系化学合成计划支持纽约州立大学奥尔巴尼分校化学系张强教授的项目。他正在开发建立多肽和蛋白质连接的最先进的方法。张教授的研究目标是建立有效和实用的方法，通过利用应变分子来合成多肽、蛋白质和糖蛋白。这项工作非常重要，因为广泛领域的科学家需要这些生物聚合物来研究植物、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制备生物大分子，这些生物大分子可用于在不同领域取得进展，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方法的开发。张教授的研究融合了有机合成、碳水化合物修饰和糖生物学的学科，为女性和其他在科学、技术、工程和数学领域历来代表性不足的学生提供了独特的教育机会。目前，化学合成多肽和蛋白质的方法很多，主要有固相合成法、天然化学连接法和无金属脱硫基等。然而，传统的合成方法有许多缺点，限制了可以生产的多肽和蛋白质的多样性和可以生产的数量。其他挑战包括所需反应步骤的数量，以及在每一步之后需要耗时的合成后提纯。通过利用β-硫代内酯及其衍生物的菌株，研究人员正在开发一种无硫酯多肽连接的方案。此外，β-硫代内酯的简单反应性使多组分一锅天然化学连接和无金属脱硫基过程能够合成复杂的蛋白质和糖蛋白。该方法的实现为以最小的分离工作量和最大的反应产量实现生物制品的化学合成开辟了一条有效的途径。此外，将不同的碳水化合物构建块安装到肽基主干中可生成具有不同糖型的均一糖蛋白；它们可用于深入评估在生物系统中重要的复杂糖蛋白。教研一体化培训正在培养一批多样化的项目学员，使他们为有利可图的职业生涯做好准备，并极大地增强他们在广泛科学领域就业机会的准备和竞争力。

项目成果

Convergent Palladium-Catalyzed Stereospecific Arginine Glycosylation Using Glycals.

使用糖基化钯催化的立体精氨酸糖基化。

• 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

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

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