Synthesis and aggregation dynamics of amylin.
| dc.contributor.advisor | Govender, Patrick. | |
| dc.contributor.author | Pillay, Karen. | |
| dc.date.accessioned | 2013-11-27T06:30:59Z | |
| dc.date.available | 2013-11-27T06:30:59Z | |
| dc.date.created | 2012 | |
| dc.date.issued | 2012 | |
| dc.description | Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2012. | en |
| dc.description.abstract | Amylin is a 37 amino acid long peptide that aggregates into toxic oligomers and fibrils. Since amylin is secreted by and also acts on pancreatic beta cells, type II diabetes is classified as an amyloidogenic disease. This study focuses on the development of a cost effective chemical synthetic strategy for amylin synthesis as previous studies relied on extremely expensive pseudoproline derivatives. Furthermore, commercially available amylin varies between batches and also contains impurities that could generate anomalies and affect reproducibility of experiments. Secondly, chemically synthesized non-methylated and N-methylated derivatives of amylin were shown to inhibit toxicity of full length amylin. A fluorescentlylabeled chemically synthesized derivative of amylin was used to track cellular localization of amylin via confocal microscopy. Amylin aggregation kinetics was established using a surface plasmon resonance (SPR) biosensor. In addition, nanoparticle tracking analysis (NTA) was used as a novel technique to determine the size of oligomers over real time. This technology indicated that the size range of the toxic species of amylin is between 200-300 nm. Furthermore, it can be suggested that NTA could potentially be developed into a screening tool for inhibitors of amylin-mediated cytotoxicity. | en |
| dc.identifier.uri | http://hdl.handle.net/10413/10076 | |
| dc.language.iso | en_ZA | en |
| dc.subject | Amylin. | en |
| dc.subject | Peptide hormones. | en |
| dc.subject | Amyloid. | en |
| dc.subject | Theses--Biochemistry. | en |
| dc.title | Synthesis and aggregation dynamics of amylin. | en |
| dc.type | Thesis | en |