The Synthesis of Carbohydrate Probes for the Diagnosis of Multiple Sclerosis
Multiple sclerosis (MS) is a neurologically debilitating disease which typically affects people in the age bracket of 27-40 years old. Currently, little is known about the mechanism of the disease, which is partly due to the lack of a reliable diagnostic test. There are two common ways of diagnosing MS, neither of which are specific to MS. One is the detection of IgG antibodies in the cerebrospinal fluid (CSF), a painful and invasive test, and the other involves obtaining MRIs of the brain to locate and monitor plaques in brain, which can be expensive and harmful. Early detection of the disease could not only lead to better symptom management, but would also allow for better monitoring of disease progress and, accordingly, lead to a better understanding of MS pathology. To this end, a reliable and non-invasive diagnostic test for the early detection of MS is required. In 2006, it was reported that antibodies against α-Glc and α-Glc(α-1,4)Glc were found at elevated levels in the sera of MS patients when compared to healthy patients’ sera, and it has been proposed that the presence of these two carbohydrates in patient serum might serve as a way to detect the onset and prognosis of MS. Accordingly, this Masters project sought to explore this hypothesis via the synthesis of α-Glc and α-Glc(α-1,4)Glc, both glycosides and glycodendrons, which could then be used to potentially detect MS-specific antibodies in sera. To this end, both glycans were prepared and coupled to biotin, ready to be used to bind streptavidin-coated enzyme-linked immunosorbent assay (ELISA) plates. An ELISA protocol is to be established by the optimisation of the negative control in order to test such glycans against plasma samples. In the hope to achieve a multivalent system, a dendrimeric scaffold was also prepared that can be used to prepare larger glycan structures for the immunodiffusion assay. Ultimately, this could lead to a new diagnostic test for MS.