Bioinspired Chemical Approach for Synthesis of Allysine Öffentlichkeit

Abstract

In this study, we present a novel chemical method for synthesizing allysine, an aldehyde containing posttranslational modification catalyzed by lysyl oxidase. This chemistry offers the ability to selectively oxidize the side chain of dimethyl lysine to allysine. Through numerous linear and cyclic peptide examples, we demonstrate the high chemoselectivity this chemical method offers, portraying its broad utility. We also expanded this chemical method for use on tertiary amine- containing small molecules. To demonstrate the applications of our method, we diversified bioactive peptides with various affinity tags and fluorescent dyes. Finally, we showcase the potential of this method for developing cellular models for studying allysine-associated diseases. 

Table of Contents

Introduction.....................................................................................................................1

Results and Discussion......................................................................................................6

Chapter 1: Background, inspiration, and approach................................................6

Chapter 2: Substrate scope of synthesizing allysine in linear and cyclic peptides...13

Chapter 3: Substrate scope for modification of small molecules...........................16

Chapter 4: Late-stage diversification of peptides via allysine with varying tags.....19

Chapter 5: Synthesis of allysine on solid support................................................20

Chapter 6: Cellular imaging applications of TACO reaction..................................23

Conclusion and Future Directions....................................................................................26

Acknowledgment of Contributions...................................................................................27

References......................................................................................................................28

Supplemental Information...............................................................................................30 

About this Honors Thesis

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School	Emory College
Department	Chemistry
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Chemistry, Biochemistry
Stichwort	Dimethyl Lysine Chemoselectivity Late-stage modification Aldehydes Protein Modification
Committee Chair / Thesis Advisor	Dr. Monika Raj, Emory University
Committee Members	Julio Medina, Emory University Dr. Christina Gavegnano, Emory University Dr. Richard Himes, Emory University

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