Morphology Engineering: Uncovering the Supramolecular Codes for Chirality 公开

Abstract

Supramolecular assemblies are found in various areas of nature, serving highly functional roles in both essential biological pathways as well as in various disease states. One notable peptide with self-assembly capabilities is Aβ42, a major isoform of amyloid β that is associated with the formation of amyloid plaques in Alzheimer’s disease. Here, characterization of various derivatives of the nucleating core of Aβ42 (Aβ16-22), including E22 (KLVFFAE), E22L (KLVFFAL), and E22V (KLVFFAV), has revealed supramolecular chiral structures with differing left- and right-handed twists. In addition to any external factors that may direct assembly chirality, we seek to uncover the design rules that dictate such inversions in peptide assemblies and establish a foundation for engineering tunable biomaterials that may be used for therapeutic purposes, including drug delivery. To achieve this, we designed a simpler peptide system where we expanded the phenylalanine sequence of the nucleating core, Aβ16-22, to a 4F system which was found to have temperature dependent supramolecular chiral inversion. The 4F system peptide was then co-assembled with Doxorubicin and subsequently heated, resulting in precise and effective drug release. The ability to engineer the morphology of these supramolecular chiral structures underscores the importance of understanding design principles as self-assembling peptides take on a greater role in the design of therapeutics and various other applications.

Table of Contents

Table of Contents

Introduction: 1

Results and Discussion: 9

-- Figure 1. Characterization of the E22 System: 10

-- Figure 2. Powder X-Ray Diffraction of the E22 System: 11

-- Figure 3. Characterization of E22L/V Co-Assembly: 12

-- Figure 4. Characterization of the E22 System with C-Terminus Modifications: 14

-- Figure 5. Heating Experiments for E22 and E22V: 15

-- Figure 6. Characterization of the 4F System with N-Terminus Modifications: 17

-- Figure 7. Characterization of the 4F System with C-Terminus Modifications and Heating: 19

-- Figure 8. TEM Progression of 4F Temperature Conversion: 20

-- Figure 9. TEM of Chymotrypsin Degradation Assay: 21

Conclusion: 23

Methods: 25

References: 36

About this Honors Thesis

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School	Emory College
Department	Chemistry
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Chemistry, Polymer
关键词	Supramolecular Chirality Chirality Inversion Peptide Helicity
Committee Chair / Thesis Advisor	Lynn, David, Emory University
Committee Members	Harmon, Brenda, Emory University Bacsa, John, Emory University

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