Novel chimeric oligonucleotides containing L-alpha-dC monomeric units linked in the 3'3' → 5 '5' orientation have been synthesized and binding studies were performed. Thermal denaturation studies done on 7-mer sequences containing either an internal 3'3' L-alpha-dC-5'5' insert or a 3'3'-D-alpha-dC-5 '5' insert in the same position, with their complementary sequence, showed a comparable destabilization of DeltaT m = 6°C and 7°C, respectively in physiological buffer. / A 19-mer sequence, complementary to a sequence near the beginning of the 5'LTR region of HIV-1 genomic mRNA, containing six alternating 3'3'-L-alpha-dC-5 '5' inserts was synthesized. Binding studies showed that this novel oligonucleotide formed stable duplexes with both its DNA and RNA targets, DeltaTm = 4°C and 8°C respectively. / Similarly, an 18-mer, also complementary to a sequence near the beginning of the 5'LTR region of HIV-1 genomic mRNA containing a terminal 3'3'-L-alpha-dC-5 '5' unit was synthesized. Binding studies demonstrated that the duplex formed showed minimal destabilization. Inhibition studies done in the presence of this modified oligonucleotide showed that the amount of (-) strong stop DNA synthesized was decreased in comparison to when the inhibition studies where done in the presence of an unmodified AON. However, due to the presence of two 5'-hydroxyl groups, this modified oligonucleotide did not serve as a substrate for the priming reaction. / The novel synthesis, as well as the characterization, of N 3-functionalized 2-beta-deoxycytidine phosphoramidite are also described.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.20286 |
| Date | January 1997 |
| Creators | Scartozzi, Margherita. |
| 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: 001608898, proquestno: MQ44275, Theses scanned by UMI/ProQuest. |
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