Enzyme-mimetic, cascade catalysis based on self-assembly of triblock polypeptides for tumor therapy

Peptide self-assembly can reproduce the structures and functionalities of the active sites of natural enzymes since they share essential similarities i.e., they are both composed of encoded amino acids and assembled through non-specific and weak supramolecular interactions. Copper metalloenzymes con...

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Main Author: Xu, Hanyan
Other Authors: Yu Jing
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2025
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Online Access:https://hdl.handle.net/10356/182926
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spelling sg-ntu-dr.10356-1829262025-03-10T06:09:24Z Enzyme-mimetic, cascade catalysis based on self-assembly of triblock polypeptides for tumor therapy Xu, Hanyan Yu Jing School of Materials Science and Engineering yujing@ntu.edu.sg Chemistry Peptide self-assembly can reproduce the structures and functionalities of the active sites of natural enzymes since they share essential similarities i.e., they are both composed of encoded amino acids and assembled through non-specific and weak supramolecular interactions. Copper metalloenzymes contain a specific ‘His-brace’ structural unit which can perform a peroxygenase catalytic pathway with the generation of hydroxyl radicals based on Fenton-type reactions. In mimicry of the functionality of ‘His-brace’, a triblock polypeptide, HxK10L10, was designed and synthesized with oligohistidines terminated block which can chelate copper ions. The self-assembly pathways of its diblock precursor (KnLm) and itself were systematically investigated i.e., the responsiveness to pH and Cu2+ ions. The assembled (Cu2+)H6K10L10 shows spherical micelles at mild acidic environments and becomes fibrils at neutral pH. Furthermore, (Cu2+)H6K10L10 can perform Fenton-type chemistry that converting hydrogen peroxide into hydroxyl radicals. Such capability can combat tumors through disrupting intracellular redox homeostasis. The treatment efficacy can be promoted by utilizing a customized nanomedicine system, (Cu2+)H6K10L10-GOx, where the administered glucose oxidase induces starvation and supplies hydrogen peroxide thereby further increasing the production of hydroxyl radicals. The synthetic triblock polypeptide as coordinated ligands can function with other metal ions or components. The metal-mediated structures and functionalities through the self-assembly can facilitate on-demand manipulation and functionalization of metallo-nanodrugs with diverse therapeutic functions. Doctor of Philosophy 2025-03-10T06:09:24Z 2025-03-10T06:09:24Z 2024 Thesis-Doctor of Philosophy Xu, H. (2024). Enzyme-mimetic, cascade catalysis based on self-assembly of triblock polypeptides for tumor therapy. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/182926 https://hdl.handle.net/10356/182926 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Chemistry
spellingShingle Chemistry
Xu, Hanyan
Enzyme-mimetic, cascade catalysis based on self-assembly of triblock polypeptides for tumor therapy
description Peptide self-assembly can reproduce the structures and functionalities of the active sites of natural enzymes since they share essential similarities i.e., they are both composed of encoded amino acids and assembled through non-specific and weak supramolecular interactions. Copper metalloenzymes contain a specific ‘His-brace’ structural unit which can perform a peroxygenase catalytic pathway with the generation of hydroxyl radicals based on Fenton-type reactions. In mimicry of the functionality of ‘His-brace’, a triblock polypeptide, HxK10L10, was designed and synthesized with oligohistidines terminated block which can chelate copper ions. The self-assembly pathways of its diblock precursor (KnLm) and itself were systematically investigated i.e., the responsiveness to pH and Cu2+ ions. The assembled (Cu2+)H6K10L10 shows spherical micelles at mild acidic environments and becomes fibrils at neutral pH. Furthermore, (Cu2+)H6K10L10 can perform Fenton-type chemistry that converting hydrogen peroxide into hydroxyl radicals. Such capability can combat tumors through disrupting intracellular redox homeostasis. The treatment efficacy can be promoted by utilizing a customized nanomedicine system, (Cu2+)H6K10L10-GOx, where the administered glucose oxidase induces starvation and supplies hydrogen peroxide thereby further increasing the production of hydroxyl radicals. The synthetic triblock polypeptide as coordinated ligands can function with other metal ions or components. The metal-mediated structures and functionalities through the self-assembly can facilitate on-demand manipulation and functionalization of metallo-nanodrugs with diverse therapeutic functions.
author2 Yu Jing
author_facet Yu Jing
Xu, Hanyan
format Thesis-Doctor of Philosophy
author Xu, Hanyan
author_sort Xu, Hanyan
title Enzyme-mimetic, cascade catalysis based on self-assembly of triblock polypeptides for tumor therapy
title_short Enzyme-mimetic, cascade catalysis based on self-assembly of triblock polypeptides for tumor therapy
title_full Enzyme-mimetic, cascade catalysis based on self-assembly of triblock polypeptides for tumor therapy
title_fullStr Enzyme-mimetic, cascade catalysis based on self-assembly of triblock polypeptides for tumor therapy
title_full_unstemmed Enzyme-mimetic, cascade catalysis based on self-assembly of triblock polypeptides for tumor therapy
title_sort enzyme-mimetic, cascade catalysis based on self-assembly of triblock polypeptides for tumor therapy
publisher Nanyang Technological University
publishDate 2025
url https://hdl.handle.net/10356/182926
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