scholarly journals Bioorthogonal Chemistry and Bioconjugation: Synergistic Tools for Biology and Biomedicine

2021 ◽  
Author(s):  
Jan van Hest ◽  
Gang Zheng ◽  
Vincent M. Rotello
Keyword(s):  
Bioorthogonal Chemistry

Suzuki–Miyaura cross-coupling for chemoproteomic applications

2020 ◽  
Author(s):  
Jian Cao ◽  
Ernest Armenta ◽  
Lisa Boatner ◽  
Heta Desai ◽  
Neil Chan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cross Coupling ◽  
Protein Profiling ◽  
Protein Labeling ◽  
Caspase 8 ◽  
Complex Cell ◽  
Bioorthogonal Chemistry ◽  
Reaction Conditions ◽  
Target Deconvolution ◽  
Palladium Catalyzed

Bioorthogonal chemistry is a mainstay of chemoproteomic sample preparation workflows. While numerous transformations are now available, chemoproteomic studies still rely overwhelmingly on copper-catalyzed azide –alkyne cycloaddition (CuAAC) or 'click' chemistry. Here we demonstrate that gel-based activity-based protein profiling (ABPP) and mass-spectrometry-based chemoproteomic profiling can be conducted using Suzuki–Miyaura cross-coupling. We identify reaction conditions that proceed in complex cell lysates and find that Suzuki –Miyaura cross-coupling and CuAAC yield comparable chemoproteomic coverage. Importantly, Suzuki–Miyaura is also compatible with chemoproteomic target deconvolution, as demonstrated using structurally matched probes tailored to react with the cysteine protease caspase-8. Uniquely enabled by the observed orthogonality of palladium-catalyzed cross-coupling and CuAAC, we combine both reactions to achieve dual protein labeling.

The Controlled Display of Biomolecules on Nanoparticles: A Challenge Suited to Bioorthogonal Chemistry

2011 ◽  
Vol 22 (5) ◽  
pp. 825-858 ◽  
Author(s):  
W. Russ Algar ◽  
Duane E. Prasuhn ◽  
Michael H. Stewart ◽  
Travis L. Jennings ◽  
Juan B. Blanco-Canosa ◽  
...  
Keyword(s):  
Bioorthogonal Chemistry

Transglutaminase-Catalyzed Bioconjugation Using One-Pot Metal-Free Bioorthogonal Chemistry

2017 ◽  
Vol 28 (10) ◽  
pp. 2518-2523 ◽  
Author(s):  
Natalie M. Rachel ◽  
Jacynthe L. Toulouse ◽  
Joelle N. Pelletier
Keyword(s):  
Bioorthogonal Chemistry ◽  
One Pot ◽  
Metal Free

Glycometabolic Bioorthogonal Chemistry‐Guided Viral Transduction for Robust Human T Cell Engineering

2019 ◽  
Vol 29 (22) ◽  
pp. 1807528 ◽  
Author(s):  
Hong Pan ◽  
Ping Li ◽  
Guifei Li ◽  
Wenjun Li ◽  
Bian Hu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Engineering ◽  
Bioorthogonal Chemistry ◽  
Human T Cell ◽  
Viral Transduction ◽  
T Cell Engineering

scholarly journals A Genetically Encoded Picolyl Azide for Improved Live Cell Copper Click Labeling

2021 ◽  
Vol 9 ◽  
Author(s):  
Birthe Meineke ◽  
Johannes Heimgärtner ◽  
Alexander J. Craig ◽  
Michael Landreh ◽  
Lindon W. K. Moodie ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mammalian Cells ◽  
Stop Codon ◽  
Bioorthogonal Chemistry ◽  
Bioorthogonal Reaction ◽  
Noncanonical Amino Acids ◽  
Selective Reactivity ◽  
Direct Incorporation ◽  
Chelating Groups ◽  
Amber Suppression

Bioorthogonal chemistry allows rapid and highly selective reactivity in biological environments. The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a classic bioorthogonal reaction routinely used to modify azides or alkynes that have been introduced into biomolecules. Amber suppression is an efficient method for incorporating such chemical handles into proteins on the ribosome, in which noncanonical amino acids (ncAAs) are site specifically introduced into the polypeptide in response to an amber (UAG) stop codon. A variety of ncAA structures containing azides or alkynes have been proven useful for performing CuAAC chemistry on proteins. To improve CuAAC efficiency, biologically incorporated alkyne groups can be reacted with azide substrates that contain copper-chelating groups. However, the direct incorporation of copper-chelating azides into proteins has not been explored. To remedy this, we prepared the ncAA paz-lysine (PazK), which contains a picolyl azide motif. We show that PazK is efficiently incorporated into proteins by amber suppression in mammalian cells. Furthermore, PazK-labeled proteins show improved reactivity with alkyne reagents in CuAAC.

scholarly journals Efficient and Flexible Synthesis of New Photoactivatable Propofol Analogs

2020 ◽  
Author(s):  
Kenneth Skinner ◽  
Joseph Wzorek ◽  
Daniel Kahne ◽  
Rachelle Gaudet
Keyword(s):  
Binding Sites ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
General Anesthetic ◽  
Bioorthogonal Chemistry ◽  
Functional Assays ◽  
Pain Pathway ◽  
Synthetic Routes ◽  
Transient Receptor ◽  
Proof Of Principle

Propofol is a widely used general anesthetic, which acts by binding to and modulating several neuronal ion channels. We describe the synthesis of photoactivatable propofol analogs functionalized with an alkyne handle for bioorthogonal chemistry. Such tools are useful for detecting and isolating photolabeled proteins. We designed expedient and flexible synthetic routes to three new diazirine-based crosslinkable propofol derivatives, two of which have alkyne handles. As a proof of principle, we show that these compounds activate heterologously expressed Transient Receptor Potential Ankyrin 1 (TRPA1), a key ion channel of the pain pathway, with a similar potency as propofol in fluorescence-based functional assays. This work demonstrates that installation of the crosslinkable and clickable group on a short nonpolar spacer at the para position of propofol does not affect TRPA1 activation, supporting the utility of these chemical tools in identifying and characterizing potentially druggable binding sites in propofolinteracting proteins.

Bioorthogonal chemistry in bioluminescence imaging

2018 ◽  
Vol 23 (9) ◽  
pp. 1584-1590 ◽  
Author(s):  
Aurélien Godinat ◽  
Arkadiy A. Bazhin ◽  
Elena A. Goun
Keyword(s):  
Bioluminescence Imaging ◽  
Bioorthogonal Chemistry

7 Tetrazine-Based Cycloadditions in Click Chemistry

2022 ◽  
Author(s):  
W. Kuba ◽  
M. Wilkovitsch ◽  
J. C. T. Carlson ◽  
H. Mikula
Keyword(s):  
Reaction Mechanisms ◽  
Chemical Biology ◽  
Bond Cleavage ◽  
Therapeutic Strategies ◽  
Complex Environments ◽  
Bioorthogonal Chemistry ◽  
Bioorthogonal Reaction ◽  
Low Concentrations ◽  
Time Critical

AbstractThe spontaneous cycloaddition of tetrazines with a number of different dienophiles has become a powerful tool in chemical biology, in particular for the biocompatible conjugation and modification of (bio)molecules. The exceptional reaction kinetics made these bioorthogonal ligations the methods of choice for time-critical processes at very low concentrations, facilitating controlled molecular transformations in complex environments and even in vivo. The emerging concept of bond-cleavage reactions triggered by tetrazine-based cycloadditions enabled the design of diagnostic and therapeutic strategies. The tetrazine-triggered activation of prodrugs represents the first bioorthogonal reaction performed in humans, marking the beginning of the era of clinical translation of bioorthogonal chemistry. This chapter provides an overview of the synthesis and reactivity of tetrazines, their cycloadditions with various dienophiles, and transformations triggered by these reactions, focusing on reaction mechanisms, kinetics and efficiency, and selected applications.

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