UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

On the self-assembly of pH-sensitive histidine-based copolypeptides

Noble Jesus, Carlos; (2020) On the self-assembly of pH-sensitive histidine-based copolypeptides. Doctoral thesis (Ph.D), UCL (University College London). Green open access

[thumbnail of Noble Jesus_10098048_Thesis_sig-removed.pdf]
Noble Jesus_10098048_Thesis_sig-removed.pdf

Download (40MB) | Preview


Over the last few decades, the field of nanomedicine has promised exciting breakthroughs for a wide range of therapeutic applications. However, there is still a need for the development of biodegradable materials, especially for applications such as drug delivery. Peptide-based nanostructures have been proposed as a promising solution, given their innate biocompatibility and biodegradability. Furthermore, the vast array of amino acids available allows for a diverse range of peptides to be constructed, with the ability to tailor their physicochemical properties to the desired application. Nevertheless, there is very limited work in this area that explores the use of peptides with physiologically relevant pH-sensitivity for targeted drug delivery. In particular, the use of polyhistidine, which features an ionisable imidazole side group whose protonated form has a pKa ≈ 6.0, in the production of vesicles remains largely unexplored despite having an ideal pH-sensitivity for use as a nanocarrier. Herein, I study the self-assembly and characterisation of amphiphilic block copolypeptides using a histidine-based hydrophobic block. The initial block copolypeptide design is inspired by block copolymers that self-assemble into vesicles. In Chapter 3, self-assembly studies are carried out to investigate pH-sensitivity and identify the resulting morphologies that are produced using techniques such as DLS and TEM. Secondary structures of these peptides are also explored using both predictive and experimental methods to better understand how the configurations they adopt affect the final self-assembled structures. The hydrophilic block is shown to have a remarkably significant impact on self-assembly of the peptide, which is designed to be driven by the hydrophobic effect upon deprotonation of the polyhistidine block. Modifications to the histidine-based block copolypeptide are also studied. In Chapter 4, the incorporation of hydrophobic amino acids into the hydrophobic polyhistidine block is shown to influence secondary structure and self-assembly behaviour. In particular, the inclusion of aromatic amino acids produces stable β-sheet structures that encourage the formation of well-defined fibrils. In Chapter 5, the effect of removing the residual terminal charge on the histidine block is also investigated by producing both acetylated and triblock variants of the histidine-based copolypeptide. Finally, the ability of both hydrophilic and hydrophobic peptides, based on the blocks used in the histidine-based copolypeptides, to form α-helices is explored via a series of simulations and circular dichroism studies in Chapter 6. The outcome of these studies show that the secondary structure of peptides with identical amino acid compositions can be significantly affected by the precise position of residues in the sequence. To this end, the work explored in this thesis shows that engineering peptides to make highly specific structures is not a trivial task.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: On the self-assembly of pH-sensitive histidine-based copolypeptides
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10098048
Downloads since deposit
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item