Studies towards peptide and protein chemical synthesis using strained thiolactones

化学系的化学合成项目支持纽约州立大学奥尔巴尼分校化学系张强教授的项目。他正在开发用于构建肽和蛋白质连接的最先进方法。张教授的研究目标是建立有效和实用的方法来合成多肽，蛋白质和糖蛋白，通过利用应变分子。这项工作非常重要，因为科学家在广泛的领域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分子生物学、细胞生物化学、农业、药物合成、医学等不同领域取得进展，以及开发多种疾病的治疗方法。张教授的研究整合了有机合成，碳水化合物修饰和糖生物学的学科，为女性和其他学生提供了独特的教育机会，历史上在科学，技术，工程和数学方面的代表性不足。目前，化学中存在多种合成方法，包括固相肽合成、天然化学连接和无金属去硫酰化，这些方法已经被开发用于获得多肽和蛋白质。然而，用于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备的量。另外的挑战包括所需的反应步骤的数量，以及在每个步骤之后需要耗时的合成后纯化。通过利用β-硫内酯及其衍生物的菌株，研究人员正在开发一种无硫酯肽连接的方案。此外，β-硫内酯的易反应性使得多组分一锅天然化学连接和无金属脱硫酰化过程能够合成复杂的蛋白质和糖蛋白。该方法的实现为生物制剂的化学合成建立了一条高效的路线，具有最小的分离努力和最大的反应输出。此外，将不同的碳水化合物构建块安装到肽基骨架中产生具有不同糖型的同质糖蛋白;它们可以用于深入评估在生物系统中重要的复杂糖蛋白。综合教育和研究培训正在培养一批多样化的项目受训人员，使他们能够从事有价值的职业，并大大提高他们在广泛科学领域就业机会的准备和竞争力。

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.