Show simple item record

dc.contributor.authorMohamady Mohamady, Samy
dc.date.accessioned2014-01-02 19:58:16 (GMT)
dc.date.available2014-05-03 05:00:26 (GMT)
dc.date.issued2014-01-02
dc.date.submitted2013
dc.identifier.urihttp://hdl.handle.net/10012/8115
dc.description.abstractNucleoside polyphosphates and their conjugates, such as nucleoside triphosphates, nucleoside tetraphosphates, sugar nucleotides, dinucleoside pyro- and higher order polyphosphates, 2’,3’-cyclic nucleoside monophosphates, and 2´-deoxynucleoside-5´-tetraphosphates in which a fluorescent label is attached to the terminal phosphate have many biological roles and have been developed into drugs. However, their synthesis remains a challenge. Several novel and efficient approaches to the synthesis of nucleoside polyphosphates and their conjugates were developed. In the first approach dinucleoside polyphosphates (NpnN’s where n = 2-4) are prepared via in situ trifluoroacetate protection and imidazolium activation of nucleoside 5’-monophosphates. This methodology was also used to prepare a substrate-intermediate analog of the reaction catalyzed by cytidine triphosphate synthase (CTPS) a recognized target for the development of antineoplastic, antiviral and antiprotozoal agents. The second approach uses sulfonylimidazolium salts as key reagents for generating highly reactive nucleotide donors. The procedure is rapid, produces a wide variety of nucleoside polyphosphates and their conjugates in high yield, does not require protection and subsequent deprotection of the nucleotide donors or acceptors and can be used to activate nucleoside mono-, di-, and triphosphates and a wide variety of acceptors. Finally an entirely new approach to the synthesis of nucleoside tetraphosphates (Np4’s), dinucleoside pentaphosphates (Np5N’s) and nucleoside tetraphosphates in which a fluorescent dye is attached to the terminal phosphate is described employing an activated form of cyclic trimetaphosphate as a novel phosphorylating agent. Attempts to prepare nucleoside triphosphates by subjecting unprotected ribonucleosides and 2’-deoxyribonucleosides to activated cyclic trimetaphosphate failed. Instead nucleoside 2’,3’-cyclic phosphates were obtained in good yield with the ribonucleoside substrates. This represents a new and convenient approach to the synthesis of this class of compounds.en
dc.language.isoenen
dc.publisherUniversity of Waterlooen
dc.subjectNucleoside polyphosphatesen
dc.subjectSulfonylimidazolium triflateen
dc.subjectDinucleoside polyphosphatesen
dc.subjectCyclic trimetaphosphateen
dc.titleSynthesis of Nucleoside Polyphosphates and their Conjugatesen
dc.typeDoctoral Thesisen
dc.pendingfalse
dc.subject.programChemistryen
dc.description.embargoterms4 monthsen
uws-etd.degree.departmentChemistryen
uws-etd.degreeDoctor of Philosophyen
uws.typeOfResourceTexten
uws.peerReviewStatusUnrevieweden
uws.scholarLevelGraduateen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record


UWSpace

University of Waterloo Library
200 University Avenue West
Waterloo, Ontario, Canada N2L 3G1
519 888 4883

All items in UWSpace are protected by copyright, with all rights reserved.

DSpace software

Service outages