Explorations of Peptide Self-Assembly in Three Chapters Open Access

Abstract

The study of biocompatible materials with implications in drug delivery, protein design and modification, and modelling of natural processes occupies a valuable niche at the intersection of many chemical, biological, and physical disciplines. Biological macromolecules are unique for their complex and intrinsic tendency to self-assemble into supramolecular morphologies that impart unique properties from linear sequences of disorganized building blocks. Access to higher order organization of peptide and peptidomimetic nanostructures begins with an understanding of the diverse set of secondary structural characteristics that can emerge from even the simplest sequences of amino acids. This work explores self-assembling peptides with design motifs based on α-helical miniproteins, polymorphic amphiphilic β-sheets, and the unique properties of β-peptide foldamers. Using a variety of biophysical techniques to optimize and delineate the properties of self-assembled oligomers, it is possible to identify trends in the sequence of synthetic polypeptides that affect resulting structure. The sequence to structure correlation of peptide nanomaterials offers insight into the quandary of the protein-folding problem and generates new tools for understanding the natural order of living systems.  

Table of Contents

Table of Contents   

Introduction 8

References 10

Chapter 1: Synthesis of Peptide-Miniprotein Conjugates 12

Introduction and Design 12

Results and Discussion 18

Peptide Synthesis and Assembly 19

Circular Dichroism 19

Transmission Electron Microscopy 20

Conclusions: 22

Materials and Methods 23

References: 25

Chapter 2: Characterization of Amphiphilic β-sheet Analogues 27

Introduction and Design 27

Results and Discussion 31

Peptide Synthesis and Assembly 31

Circular Dichroism 32

Transmission Electron Microscopy 36

Conclusions: 45

Materials and Methods 47

References: 49

Chapter 3: Development of Novel Self-Assembling β-Peptide Foldamer Oligopeptides 52

Introduction and Design 52

Results and Discussion 61

Peptide Synthesis and Assembly 61

Circular Dichroism 61

Transmission Electron Microscopy 62

Conclusions: 66

Chapter 3: Solving the Structure of a β-Peptide Foldamer Nanotube 68

Introduction 68

Results and Discussion 68

Peptide Synthesis and Assembly 68

Transmission Electron Microscopy 69

Future Steps: 69

Materials and Methods 70

References: 73

About this Honors Thesis

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School	Emory College
Department	Chemistry
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biophysics, General Chemistry, Polymer Chemistry, Biochemistry
Keyword	Amyloid Self-Assembly Foldamer
Committee Chair / Thesis Advisor	Vincent Conticello, Emory University
Committee Members	Richard Himes, Emory University Kate O'Toole, Emory University

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