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.
