The unique architecture of branched oligonucleotides was exploited to study compounds that associate as two parallel duplexes with intercalating C•C+ base pairs (i-motif DNA). The formation of a branched cytosine tetrad was induced by joining the 5'-ends of a pair of pentadeoxycytidine strands with a branching riboadenosine (rA) linker. This arrangement causes the orientation of the dC strands to be parallel, and forces the formation of a C•C+ duplex that self associate into i-DNA. Presence of the i-motif in this structure is supported by thermal denaturation, native gel electrophoresis, CD, and NMR spectroscopy. / To further characterize the nature of the sugar-sugar interactions in the i-motif, branched oligonucleotides containing D-arabinocytidine and D-ribocytidine were synthesized and their association properties examined. The branched D-deoxycytidine analogue, rA(2',5'-dC 5)-3',5'-dC 5 (dV-5) served as model system. It is found that the arabinose substitution leads to hypochromic structures that are characteristic of four-stranded intercalated DNA and has little, if any, effect on the stability of the complex formed. Parallel experiments with the branched ribocytidine analogs gave very weak or no discernible UV transitions, consistent with no strand association in this case. These results are discussed in relation to expected steric interactions of oligocytidine strands within the 1-motif. / A divergent approach for the construction of branched nucleic acids was also studied. Chain assembly took place on the surface of controlled-pore glass solid support in the unconventional 5' to 3 ' direction. The branch junctures were introduced by use of N6-benzoyl-2',3'-O-bis(dimethoxytrityl)adenosine-5 '-O-(N,N-diisopropyl)-beta-cyanoethylphosphoramidite. Various dendrimers were prepared in comparable or better yields relative to the well-established convergent approach.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.35931 |
| Date | January 1999 |
| Creators | Robidoux, Sébastien. |
| Contributors | Damha, Masad 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 | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001655197, proquestno: NQ50245, Theses scanned by UMI/ProQuest. |
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