University of Illinois Urbana-Champaign

The α-helical conformation of polypeptides: design, regulation, and applications

Song, Ziyuan

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SONG-DISSERTATION-2017.pdf

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https://hdl.handle.net/2142/97553

Description

Title
The α-helical conformation of polypeptides: design, regulation, and applications
Author(s)
Song, Ziyuan
Issue Date
2017-04-13
Director of Research (if dissertation) or Advisor (if thesis)
Cheng, Jianjun
Doctoral Committee Chair(s)
Cheng, Jianjun
Committee Member(s)
  • Zimmerman, Steve C.
  • Ferguson, Andrew L.
  • Leal, Cecilia
Department of Study
Materials Science & Engineerng
Discipline
Materials Science & Engr
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2017-08-10T19:51:48Z
Keyword(s)
  • Polypeptide
  • α-helix
  • 1,2,3-triazole
  • Helix-coil transition
Abstract
Synthetic polypeptides have received increasing attention during the past two decades. Compared to other synthetic polymers, polypeptides share the same peptide backbones with naturally-occurring proteins, which allows them to form higher order structures spontaneously and enables their unique performance as biomaterials. For instance, the α-helical conformation, one of the most important secondary structure motifs, is found in both proteins and polypeptides. Polypeptide materials with α-helical structures exhibit interesting properties in cell penetration field, self-assembly, as well as molecular catalysis, mainly due to the separated backbone-side chain (core-shell) structure, the anisotropic alignment of rigid rod-like geometry, and the macrodipoles, respectively. The goal of my Ph.D. research is focused on the design, regulation, and applications of polypeptide α-helices. In the first part of this dissertation, we developed a new strategy to regulate the conformation of polypeptides by directly manipulating the backbone hydrogen bonding interactions. Specifically, 1,2,3-triazole groups were incorporated on the side chains of polypeptides, which serve as both hydrogen bond donors and acceptors at neutral and basic pH to disrupt the α-helical structure, while lose their disrupting ability when protonated at acidic pH due to their inability to act as hydrogen bond acceptors. The triazole-based polypeptides therefore exhibited reversible, pH-responsive helix-coil transition behavior, which was demonstrated by spectroscopic method, molecular dynamics simulation, as well as small angle neutron scattering technique. The second part of this dissertation focused on the applications of α-helical polypeptides in cell penetration and self-assembly field. The above-mentioned triazole polypeptides were first used as smart cell-penetrating peptide mimics, whose membrane activity is correlated with the pH value due to the conformation change. When coupled with other targeting ligands, these polymers showed cancer cell-specific internalization followed by acid-activated endosomal escape. The conformation-associated cell-penetration ability was also demonstrated with another series of cationic polypeptides bearing phosphonium side chains, which serve as promising molecular transporters due to the low cytotoxicity of phosphonium-related biomaterials. Finally, α-helical polypeptides with hydrophobic side chains were studied as building blocks for vesicular self-assembly. Polymersomes with densely packed multilayer membrane structures were observed when PEG was used as the randomly coiled hydrophilic block.
Graduation Semester
2017-05
Type of Resource
text
Permalink
http://hdl.handle.net/2142/97553
Copyright and License Information
Copyright 2017 Ziyuan Song

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Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Materials Science and Engineering