Peptide self-assembly in biomaterial design

• Main Author: Currie, Keith William John
• Published: Queen's University Belfast 2014
• Subjects: 615
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.673801

The process of self-assembly of short synthetic peptides into highly complex organised hydrogel structures is currently of interest due to the fact that these can potentially form a commercially viable means of producing novel biomaterials with a diverse range of functions and applications in drug delivery and tissue engineering. This thesis aimed to design a range of bespoke short synthetic peptides and examine the effects of varying the chemistry of the N-terminus on the ability of certain dipeptide sequences to form competent hydrogelators. As the design of competent peptide hydrogelators from first principles remains a challenge in this field, an examination of the effects of N-terminus chemistry was warranted to further understand the role that the N-terminus plays in either aiding or hindering dipeptide self-assembly. Following the successful solid-phase synthesis ofa library of twenty-eight dipeptides, these compounds were tested for their ability to form hydrogels following gelation triggering using solvent based induction using DMSO and via a pH change based induction using G1ucono-delta-lactone (GdL). Eleven successful hydrogelators were identified in the DMSO induction tests and hydro gels formed using this method were assessed for secondary structure, micro-morphology and mechanical properties using FTIR, TEM and rheology respectively. The presence of aryl-oxyethyl carbonyl and ethyl carbonyl linkers in the N-terminus appeared to hinder gelation via DMSO triggering. Twenty successful hydrogelators were identified when GdL was used to cause a pH change induction. The presence of oxyethyllinker groups in the N-terminus also appeared to hinder the gelation of compounds when using pH induction. Following the analysis of the secondary structure and mechanical properties of hydro gels formed using DMSO or pH induction methods, the compounds were then tested for in vitro cytotoxicity towards the human cell lines HeLa and HaCaT. Several novel compounds were identified as candidates for further in vitro and in vivo studies.