This fast-track STTR application proposes to synthesize structurally defined heparan sulfate and chondroitin sulfate oligosaccharides for biological research. Glycan Therapeutics is a biotech company specializing sulfated carbohydrates using innovative enzyme-based methods. This proposal is focused on the synthesis of large authentic oligosaccharides in the size range of 10-mers to 16-mers, as well as ultra-large click oligosaccharides in the size range of 30 saccharide residues long. A highly experienced research team, including Dr. Yongmei Xu (University of North Carolina), Dr. Robert Linhardt (Rensselaer Polytechnic Institute), and Dr. Vijayakanth Pagadala (Glycan Therapeutics), will carry out the study. Heparan sulfate and chondroitin sulfate are members of the glycosaminoglycan family present in large quantities on mammalian cell surfaces and in the extracellular matrix, displaying a wide range of biological functions. This proposal is designed to serve two purposes: (i) to develop a reliable and cost-effective method to synthesize structurally defined heparan sulfate and chondroitin sulfate oligosaccharides and structurally controlled polysaccharides to support glycoscience research; and (ii) to simplify this technology to allow non-glycoscientists to utilize this technology in a standard biochemistry laboratory setting.
Three specific aims are proposed:
Aim 1 is to synthesize a library of structurally defined heparan sulfate oligosaccharides with a size of up to hexadecasaccharides (16-mers);
Aim 2 is to develop novel chemoenzymatic methods to synthesize chondroitin sulfate oligosaccharides;
Aim 3 is to prepare structurally controlled click heparan sulfates and chondroitin sulfate oligosaccharides. In Phase I we will demonstrate the feasibility of making a limited number of larger heparin sulfate and chondroitin sulfate oligosaccharides and then click these larger oligosaccharides together to make ultra-large compounds. In Phase II we will make additional larger compounds and again click these to make ultra- large oligosaccharides. We will then make ?do-it-yourself? ligation kits available commercially. We anticipate that this proposal will provide valuable technical advances to glycoscience research.
Heparan sulfate and chondroitin sulfate are biologically important poylsaccharides in humans. This project aims to develop enzyme-based methods to synthesize both heparan sulfate and chondroitin sulfate. The outcome from this project will offer a wide range of heparan sulfate and chondroitin sulfate compounds for biochemcial studies and to aid in the developmeny carbohydrate-based medicines.