The Dong Research Group

at Peking University School of Pharmaceutical Sciences

Organic synthesis is an important discipline which plays a key role in drug discovery and in the allied fields of medicine and biology. Conventionally, natural products have been referred as small molecules that were extracted from plants, marine organisms, or microorganism fermentation broths. However, considering natural product as a compound produced by a living organism, in a broader sense, the concept of “natural product” may be extended to include biological level molecules such as polypeptides, proteins, and glycoproteins. As the increased development and growth of biomedicines (e.g., hormonal drugs) has been playing more and more important roles in the treatment of human disease, the use of polypeptides and proteins has further broadened and emphasized the role of natural product in pharmaceutical drug discovery and drug design. Accordingly, it is necessary to expand the concept of “total synthesis”, and extend the reach of chemical synthesis from “small molecules” to large “biologics”. This proposed research program will focus on the synthesis of natural occurring targets possessing promising biological activities, and the utilization of the developed synthetic routes to prepare natural product-derived analogues, which could be potentially valuable drug candidates. Along the theme of total synthesis, we will also investigate and develop novel chemical synthesis methods and enabling approaches to the chosen bioactive targets, including asymmetric syntheses of small molecule natural products, synthesis of homogeneous glycoprotein containing -linked sialo-oligosaccharides, etc. Moreover, we will utilize the prepared materials in hand to answer fundamental questions, such as roles of glycosylation in proteins, and to explore mechanism of action of those compounds in strategic biological collaborations.

Glycosylation is one of the most common and highly diverse post-translational modifications for proteins, and plays important roles in mediating protein folding, in protecting protein against proteolysis, in cellular differentiation, and in cell-cell communication. While glycoproteins are crucial in many biological processes, it has been a challenge to study and understand the functions associated with specific glycoforms, due to the highly complex and inseparable mixture of various glycoforms of mammalian cell-expressed glycoproteins. Thus, an access to homogeneous glycoproteins will be of great value in exploring the functions of specific glycoforms, such as structure-activity relationship (SAR).