Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558793
Title: Self-assembly of peptides and peptide based hybrids for therapeutic applications
Author: Krysmann, Marta J.
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2009
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Abstract:
A rich gallery of novel systems based on the sequence KLVFF (namely KLVFF, FFKLVFF, AAKLVFF, AAKLVAA, βAβAKLVFF, KLVFF-PEG, FFKLVFF-PEG, AAKLVFF-PEG, AAKLVAA-PEG, FF-PEG, FFFF-PEG) was synthesized and characterized. For the first time structure-properties relationships of this class of materials were systematically explored, with emphasis on self-association properties in both bulk and solution. Such a comparative investigation, essentially absent from the literature, provides insights into the underlying mechanism of amyloid fibrogenesis, given that KL VFF has been identified as critical for amyloid fibril formation of the amyloid-β peptide. In this respect, this virtually unique, bottom-up approach contributes to the development of therapeutics for Alzheimer's disease. Despite the fact that all the peptides were found to organize into predominantly β-sheet conformations (in a variety of solvents and in bulk) they exhibit a versatile range of morphological features, such as fibrils, twisted assemblies of protofilaments, hollow tubes and single tapes. Interestingly, FFKLVFF was found to exhibit strong fibrillization properties, while helically twisted ribbons were obtained from βAβAKL VFF. The self-organization of KLVFF towards fibrillar symmetries gives rise, under certain conditions, to time-dependant hydrogels with potential for application in tissue engineering. Notably, only FFKLVFF-PEG and FFFF-PEG retain the β-sheet conformation of the peptide precursor, and they form fibrils bearing a peptidic core surrounded by a corona of PEG chains. At high volume fractions packing of the FFKLVFF-PEG fibrils leads to the evolution of nematic and hexagonal columnar phases. Owing to their inherent biocompatible character, those hybrids carry great promise to substitute a number of conventional polymers in applications such as tissue engineering, cell growth and drug delivery. In the solid state, the interplay between two competing factors, polymer crystallization and peptide fibrillization, was studied for several conjugates. Two distinct cases were identified; solidification of FFKL VFF-PEG controlled by peptide- peptide interactions, while KLVFF -PEG and AAKL V AA-PEG crystals reflected the characteristics of PEG spherulites.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.558793  DOI: Not available
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