Development of a GBP-based glycosylation analysis system

Project Summary / Abstract The surface of cells and proteins are decorated with complex polysaccharide modifications (glycans) which help shape identity, function, and immunogenicity. Glycans have been shown to play major roles in diseases such as cancer and in the function and stability of therapeutic proteins. Research on glycan structures is challenging and expensive, requiring specialized equipment and large amounts of samples to obtain functional structural isomeric information. Using glycan binding proteins to assay glycan structure is a rapid and affordable option for glycan isomeric structural analysis but there is no software capable of providing automated analysis of the data. To meet this need, two groups with a history of implementing transformative glycan assay and software solutions will improve upon glycan binding assays offered by Z Biotech LLC and optimize the glycan structure analysis with a prototype software developed by the Haab laboratory. Preliminary analysis with the software has already demonstrated remarkable ability to predict glycan structural features from purified glycoproteins and biological samples but has revealed limitations that this work will address. In the Phase I of this SBIR project, we will address these limitations in three aims: 1) We will supplement and improve the available data used for predicting binding by collecting a large glycan array dataset with a wide dynamic range for accurate estimates of binding affinity; 2) We will expand our coverage of glycan epitopes by supplementing with additional lectins and antibodies; 3) We will optimize the algorithm for different glycan binding assays by using control glycans to account for phase shifts in affinity specific to the platform. This work will transform glycan structure analysis by offering a new low-cost glycan isomeric structure analysis platform which will open up new opportunities for clinical and pharmaceutical research.