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Development of a New General Click Chemistry and Applications in Bioconjugation: Part I: Rewiring Bacteria Cell Surfaces with Bio-Orthogonal Chemistry Part II: A Novel General Dialdehyde Click Chemistry for Primary Amine Conjugation

Development of a New General Click Chemistry and Applications in Bioconjugation: Part I: Rewiring Bacteria Cell Surfaces with Bio-Orthogonal Chemistry Part II: A Novel General Dialdehyde Click Chemistry for Primary Amine Conjugation

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Title: Development of a New General Click Chemistry and Applications in Bioconjugation: Part I: Rewiring Bacteria Cell Surfaces with Bio-Orthogonal Chemistry Part II: A Novel General Dialdehyde Click Chemistry for Primary Amine Conjugation
Author: Elahipanah, Sina
Abstract: The ability to tailor cell surfaces with non-native molecules is critical to advance the study of cellular communication, cell behavior, and for next-generation therapeutics. There has been tremendous effort to tailor mammalian cell surfaces with organic functional groups; however, there are few reliable and non-invasive methods for re-wiring the bacterial cell surface. Current methods to re-engineer bacteria surfaces rely on complicated, slow, and often expensive molecular biology and metabolic manipulation methods with limited scope on the type of molecules installed onto the surface. In the first part of this report, we introduce a new straightforward method based on liposome fusion to re-engineer Gram-negative bacteria cell surface with bio-orthogonal groups that can subsequently be conjugated to a range of molecules (biomolecules, small molecules, probes, proteins) for further studies and programmed behavior of bacteria. This method is fast, efficient, inexpensive, and useful for installing a broad scope of ligands and biomolecules to Gram-negative bacteria surfaces.
The development of methods to conjugate a range of molecules to primary amine functional groups have revolutionized the fields of chemistry, biology and material science. Due to its abundance, the primary amine is the most convenient functional group handle in molecules for ligation to other molecules for a broad range of applications that affect all scientific fields. Current conjugation methods with primary amines include the use of activated carboxylic acids, isothiocyanates, Michael addition type systems and reaction with ketones or aldehydes followed by in situ reductive amination. In the second part, we introduce a new traceless, high yield, fast; click chemistry method based on the rapid and efficient trapping of amine groups via a functionalized dialdehyde group. The click reaction occurs in mild conditions in organic solvents or aqueous media, proceeds in high yield. Moreover, no catalyst or activating group is required and the only by-product is water. The dialdehyde headgroup was used for applications in cell surface engineering and for tailoring surfaces for material science applications. We anticipate broad utility of the general dialdehyde click chemistry to primary amines in all areas of chemical research ranging from polymers, bioconjugation to material science and nanoscience
Subject: Biochemistry
Keywords: Organic Chemistry
Click Chemistry
Bioconjugation
Amine Conjugation
Amine Bioconjugation
Primary Amine Bioconjugation
Amine Coupling
Lysine Conjugation
Liposome Fusion
Functionalized Liposome
Oxime
Hydroxylamine
Ketone
Hydrazone
Traceless Bioconjugation
Enamine formation
1
4 dihydropyridine
Cell Surface Engineering
Bioorthogonal Chemistry
Bacteria
Protein Crosslinking
Material Science
Cell Immobilization
Dialdehyde
Lipid
Antibody Drug Conjugate
Medicinal Chemistry
Adjuvants
Physical Chemistry
Synthesis
Characterization
Spectroscopy
Nuclear Magnetic Resonance
Mass Spectrometer
Immunology
Biotin
Streptavidin
Antibiotics
Reversible Reaction
Surface Chemistry
Oxidative Cleavage
Convergent Synthesis
Amide formation
Peptide Coupling
Fluorescent Probe.
Type: Electronic Thesis or Dissertation
Rights: Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
URI: http://hdl.handle.net/10315/34274
Supervisor: Yousaf, Muhammad N.
Degree: PhD - Doctor of Philosophy
Program: Chemistry
Exam date: 2017-05-04
Publish on: 2018-03-01

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