The use of chemically modified oligonucleotides (AON) to selectively inhibit the expression of genes involved in pathological processes, offers a rational approach for the prevention and treatment of some disorders. Phosphorothioate oligonucleotides (PS-DNA), in which one of the non-bridging oxygen atoms of the internucleotide linkage is replaced by a sulfur atom, have been extensively studied and are among the most widely used "antisense" oligonucleotides (AON). However, the isomeric analogue, in which one of the two bridging oxygen atom is replaced by sulfur has not been extensively investigated, as such, this prompted our interest towards the construction of oligonucleotides containing the modified 3'-S- and 5'-S-phosphorothiolate linkages. An oligodeoxynucleotide (DNA) strand containing a single and three consecutive 3'-and 5'-S-phosphorothiolate internucleotide linkages as well as a chimeric oligonucleotide, composed of 2'-OMe-RNA 'wings' with a central hexanucleotide ("gap") composed of 3'-deoxy-3'-thiothymidine (T3'S) residues were successfully prepared via the phosphoramidite approach. (Abstract shortened by UMI.)
Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.81445 |
Date | January 2004 |
Creators | Tedeschi, Anna Lisa |
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: 002178389, proquestno: AAIMR06460, Theses scanned by UMI/ProQuest. |
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