Engineered Peptide Platforms: Design, Synthesis and Application

Choi, Wonmin

doi:https://doi.org/10.21985/n2-yp5f-0z54

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Engineered Peptide Platforms: Design, Synthesis and Application

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Peptides consists of a series of amino acids connected via an amide type of covalent chemical bond. A diverse field of applications such as biosensors,2 catalysis,4 and biomedicine6 include the oligomeric forms of peptides due to their genuine features comparing to other biomacromolecules. Particularly, peptides in the field of biomedical application have garnered much interest due to their biocompatibility, high selectivity, and potency. Different platforms and technologies have been adopted to improve efficacy or expand the versatility of peptides. Peptide hydrogels, for example, have a three-dimensional fibrillar network structure employing self-assembly of peptides. Due to their low toxicity and biodegradability, peptide hydrogels have been widely used in different biomedical application such as drug delivery,7 protein separation,8 biosensors,9 tissue engineering,10 and wound healing.11 The protein-like polymer (PLP) is another class of peptide employing platform where peptides are densely arranged onto a hydrophobic polymer backbone, giving a globular structure similar to natural proteins. PLPs show unique properties compared to other peptide based therapeutics such as increased cellular uptake or enhanced enzyme resistance, thus opening a new opportunity for therapeutic peptide delivery. This thesis explores the diverse peptide platforms from biological signal responsive peptide materials to the PLP as a novel technology for peptide drug delivery. In Chapter 1, a brief introduction of different engineered peptide platforms will be discussed. In Chapter 2 and 3, the pH-responsive charge conversion peptide pro-gelators and light-activatable enzyme responsive nanoparticles are described, respectively, as advanced design of stimuli-responsive peptide materials. In Chapter 4, the backbone effect of PLPs to enzyme resistance is discussed. Enzyme resistance of PLPs with different backbone structures is further demonstrated by both experimental results and computational simulations. A new synthetic route for PLPs is introduced in Chapter 5. PLP synthesis with photo-induced electron/energy transfer-reversible addition-fragmentation chain transfer polymerization (PET-RAFT) provides mild and environmentally friendly polymerization methods. Finally, therapeutic application of PLPs to treat Huntington’s Disease (HD) and neovascular age-related macular degeneration (nAMD) will be discussed in Chapter 6 and 7.

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