Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.663788
Title: Synthesis and applications of disulphide containing oligonucleotides
Author: Wilkinson, Adrian J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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Abstract:
A novel disulphide containing phosphotriester monomer has been synthesised which possesses oligonucleotide coupling efficiencies which are superior to those obtained from existing disulphide monomers. This dipropyl disulphide linker, which should be stable outside the cell but vulnerable to disulphide cleavage by thiols contained in the cell, has been introduced between the lipophilic groups and oligonucleotides. The oligonucleotides should thus be released from the lipophilic groups once endocytosis has occurred. Similarly, the dipropyl disulphide linker has been introduced between a biotin group and an oligonucleotide. Quantitative disulphide cleavage can be achieved by the addition of dithiothreitol. Thus oligonucleotides bearing cleavable biotin moieties have been synthesised, employing a far more facile and high yielding process than the current method of choice. This approach has been extended to the synthesis of a novel amino functionalised disulphide linker for the production of the first cleavable aminolink oligonucleotides. Cleavage of the disulphide bond in the dipropyl disulphide linker produces a propyl thiol group at the 5'-end of an oligonucleotide. A diethyl disulphide linker has been synthesised which produces an ethyl thiol group on the oligonucleotide after disulphide cleavage. Under basic conditions, the oligonucleotide can eliminate mercaptoethanol to give a 5'-phosphate group. Thus a simple, high-yielding method for the synthesis of terminal thiol and terminal phosphate functionalised oligonucleotides has been developed, offering a viable alternative to existing routes to these functionalities.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.663788  DOI: Not available
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