A method to synthesize a diastereomeric mixture of 2',5 '-phophorothioate A(psG) dimers in solution was developed. The sulfurizing reagent "EDITH" allowed for the synthesis of the diastereomeric mixture of dimers with minimal formation of oxidized side products. The separation of the two isomers was carried out using silica gel flash chromatography to afford the stereoisomerically pure Rp and S p dimers. The orthogonal solution-phase coupling of the individual dimers to the appropriately protected monomers allowed for the creation of the corresponding branched trimers bearing vicinal 2',5'-phophorothioate and 3',5'-phosphodiester linkages. / Conversely, a convergent solid-phase strategy applicable to the synthesis of branched oligonucleotides was employed to construct a symmetrical branched phosphodiester trimer, A(pG)pG, using an adenosine bisphosphoramidite synthon. This compound served as a positive control substrate, relative to both the Sp and Rp-phophorothioate V-trimers, in the investigation of the stereochemical requirements of the yeast debranching enzyme (yDBR) at the 2',5'-phosphodiester linkage. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.29458 |
| Date | January 2002 |
| Creators | Mourani, Rawan |
| Contributors | Damha, M. J. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001957140, proquestno: MQ85809, Theses scanned by UMI/ProQuest. |
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