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Title: Synthesis and biological activity of some specialised minor groove binders
Author: Breen, David
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2008
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Minor groove binders (MGBs) are molecules which bind selectively to the minor groove of DNA. Distamycin 1 and netropsin 2 are naturally occurring MOBs, and are members of the polypyrrole class of compounds. These compounds consist of two and three methylpyrrole monomers linked by ami des, with a head and tail group also linked by amides. They have potential antiviral, antibiotic, and antioncolytic properties, however they are also toxic. These biological effects arise from the molecule binding to DNA in regions where there are short runs of A:T base pairs. Much work has been carried out to develop analogues of distamycin 2 and netropsin 1 which have improved biological activity and a reduced toxicity profile. This project will be concerned with developing a novel solid-phase/parallel synthesis of MGBs which allows for more varied substituents at the tail end of these molecules which, to date, has not been fully investigated. The tail group is significant as it plays a key role in both DNA binding, and transportation of these compounds to within cells. The second aim of this project is to develop and synthesise a range of MGBs which will link the head group and/or heterocyclic monomers via an alkene linker, replacing the typical amide links, this should give these compounds enhanced Lipophilicity and in turn better membrane permeability which we hope will result in more active antibacterial compounds. These compounds are also of interest as they are expected to be intrinsically fluorescent; this may allow these compounds to have a range of further application other than as antibacterial agents, as potential analytical tool for example as molecular stains etc.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available