Design and synthesis of protein mimetics via living polymerization of β-sheets-forming n-carboxyanhydride

Proteins are one of the most important biomacromolecules which play important roles in various cellular activities such as enzyme catalysis, signal transduction and transmembrane transportation. In the past several decades, various approaches have been explored to prepare peptides or polypeptides materials, aiming to synthetically mimic the architecture and function of proteins. Among all well-established method, N-carboxyanhydride (NCA) chemistry is able to provide synthetic polypeptides in high molecular weights. And the recent development of functional NCA monomers and the post-modification strategy make it practical to conjugate non-natural function groups on the synthetic polypeptides. However, till now, though the multi-chains assembly from synthetic polypeptides has been investigated, the protein-like single-chain folding based on synthetic polypeptides as protein mimetics has never been studied. The goal of my Ph.D. research is focused on the synthesis, regulation, and applications of polypeptide from the polymerization of β-sheets-forming NCAs (NCAs that form synthetic polypeptides in β-sheets conformation) and push a synthetic polypeptides system to their limitation as artificial protein mimetics. As a structural domain in proteins that play important roles in their folding process, it has been a challenge for a long time to obtain polypeptides in β-sheets conformation in a controlled and convenient manner. In the first part of this dissertation, I deeply investigated the polymerization of β-sheets-forming NCAs, and I established a living polymerization strategy. The second part of this dissertation focused on the design and synthesis of multiblock co-polypeptides with high content of β-sheets that mimic the structure and folding mechanism of proteins with tandemly repeating domain. A strategy to fabricate polypeptide nanoparticles from the folding of single polypeptide chain was developed by tuning the self-assemble of interdomain β-strands within one polypeptides chain. In the third part of my work, inspired by the mechanism of green fluorescent proteins, I trapped a dye molecule inside the hydrophobic β-sheets core of the synthetic single-chain polypeptides nanoparticle, I successfully fabricated a synthetic analog to green fluorescent proteins. Two more independent works were also recorded in the final part of this dissertation. One is about the living polymerization of a functional β-sheets-forming NCA, and the other is about a streamlined strategy to synthesize PEG-polypeptides directly from amino acids.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Xue, Tianrui

Contributors dc:contributor

• Braun, Paul V.
• Cheng, Jianjun
• Zimmerman, Steven C.
• Evans, Christopher M.

• Polypeptides
• N-Carboxyanhydride
• Single-Chain Nanoparticles
• Protein Mimetics
• Secondary Structures

Statement dc:rights

• Copyright 2022 Tianrui Xue

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/115920

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F115920