The development of STICS (Surface Tethered Iterative Carbohydrate Synthesis), a new approach to the supported synthesis of oligosaccharides, will be pursued. The approach is based on the use of porous gold, chosen for its extremely high surface area and chemical stability. The porous gold films will be created on titanium foil, and then characterized using electron microscopy and electrochemistry. The gold surfaces will then be modified with self-assembled monolayers of tri-thiolated derivatives designed to be stable in organic solvents and provide an initial layer of amine groups for initiation of the step-wise synthetic process. The monolayer surface coverage will be characterized using electrochemistry and solution-depletion measurements using UV-visible spectroscopy. Upon proving the feasibility of the surface modification, our attention will be turned to the development of a new glycosylation methodology on the surface. Novel glycosyl donors, S-benzoxazolyl (SBox) glycosides, will be used for both the attachment of the first monosaccharide and the oligosaccharide chain elongation. At the end of the sequence, the assembled glycostructures on the solid support will be deprotected and made usable for subsequent biological testing. The supports will be stacked in a manner suitable for the creation of small combinatorial libraries of compounds. It is envisioned that these very high surface area supports will be usable in molecular recognition studies using solution depletion measurements and standard assays of protein concentration. The potential application of these supports in ELISA methods will be explored. Relevance: Recognition of the significance of carbohydrate structures in human biology has been growing rapidly in recent years, especially in areas such as immunity and cancer. Lipids and proteins are often found with unique carbohydrate structures attached to them that are crucial for their function. In order to study the ultimate medical significance of these carbohydrates, new approaches are needed to synthesize them and study their behavior. ? ? ?
| Lee, Jinwoo; Nyenhuis, David A; Nelson, Elizabeth A et al. (2017) Structure of the Ebola virus envelope protein MPER/TM domain and its interaction with the fusion loop explains their fusion activity. Proc Natl Acad Sci U S A 114:E7987-E7996 |
| Pornsuriyasak, Papapida; Ranade, Sneha C; Li, Aixiao et al. (2009) STICS: surface-tethered iterative carbohydrate synthesis. Chem Commun (Camb) :1834-6 |
| Parlato, M Cristina; Kamat, Medha N; Wang, Haisheng et al. (2008) Application of glycosyl thioimidates in solid-phase oligosaccharide synthesis. J Org Chem 73:1716-25 |
| Shulga, Olga V; Jefferson, Kenise; Khan, Abdul R et al. (2007) Preparation and Characterization of Porous Gold and its Application as a Platform for Immobilization of Acetylcholine Esterase. Chem Mater 19:3902-3911 |
