The investigation and development of IGD peptidomimetics as wound healing agents

Matheson, Mhairi (2015) The investigation and development of IGD peptidomimetics as wound healing agents. PhD thesis, University of Glasgow.

Due to Embargo and/or Third Party Copyright restrictions, this thesis is not available in this service.

Abstract

An ever increasing incidence of diabetes has resulted in an epidemic of chronic wounds. Few therapies effectively promote wound healing, and thus, health care budgets are faced with an unsustainable burden and patients with poor quality of life. Recently, the isoleucine-glycine-aspartic acid (IGD) tripeptide motif of Migration Stimulating Factor (MSF) has been found to be responsible for the wound healing properties of this protein. Modelling studies of the IGD motif of MSF have lead to the design and synthesis of a benzodiazepinone core, which displays wound healing properties in vitro and in vivo. This thesis discusses the optimisation of the synthetic route to this exciting IGD peptidomimetic and investigations into the activity and the method of action of this molecule through scratch assays and qRT-PCR studies. Analogues of this benzodiazepinone with varying synthetic handles have been developed and used to tag the active bicyclic core with desired technologies. In one such example, BODIPY tagging and confocal microscopy allowed the investigation of fibroblast uptake of the BODIPY IGD peptidomimetic. An IGD peptidomimetic with a triethylene glycol synthetic handle has been developed for increased hydrophilicity and is envisioned to be used in the development of a therapeutic hydrogel.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Diabetes, wound healing, IGD, tripeptide, peptidomimetic, Migration Stimulating Factor, Fibronectin, organic synthesis, BODIPY, fluorophore, benzodiazepinone, cell migration, cell motility
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Funder's Name: UNSPECIFIED
Supervisor's Name: Rudi, Dr. Marquez
Date of Award: 2015
Embargo Date: 2 November 2018
Depositing User: Dr Mhairi Matheson
Unique ID: glathesis:2015-6810
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 03 Nov 2015 10:16
Last Modified: 05 Nov 2015 16:29
URI: http://theses.gla.ac.uk/id/eprint/6810

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