Tumor-Acidity and Bioorthogonal Chemistry-Mediated On-Site Size Transformation Clustered Nanosystem to Overcome Hypoxic Resistance and Enhance Chemoimmunotherapy

ACS Nano ◽  
2022 ◽  
Author(s):  
Kewei Wang ◽  
Maolin Jiang ◽  
Jielian Zhou ◽  
Ye Liu ◽  
Qingyu Zong ◽  
...  
Keyword(s):  
Bioorthogonal Chemistry ◽  
Tumor Acidity ◽  
Hypoxic Resistance

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.

Cisplatin Resistance Reversal of Lung Cancers by Tumor Acidity-Activable Vesicular Nanoreactors via Tumor Oxidative Stress Amplification

2021 ◽  
Author(s):  
Jean Felix Mukerabigwi ◽  
Yu Han ◽  
Nannan Lu ◽  
Wendong Ke ◽  
Yuheng Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Therapeutic Efficacy ◽  
Cisplatin Resistance ◽  
Clinical Applications ◽  
Lung Cancers ◽  
Resistance Reversal ◽  
Tumor Acidity ◽  
Stress Amplification ◽  
Novel Strategy

Drug resistance of cisplatin significantly limits its therapeutic efficacy in clinical applications against a variety of cancers. Herein, we develop a novel strategy to overcome cisplatin drug resistance through sensitizing...

scholarly journals Tumor acidity-induced charge-reversal liposomal doxorubicin with enhanced cancer cell uptake and anticancer activity

Giant ◽  
2021 ◽  
Vol 6 ◽  
pp. 100052 ◽  
Author(s):  
Jinpeng Yang ◽  
Zihe Yin ◽  
Yincheng Chang ◽  
Hua Wang ◽  
Jiang-Fei Xu ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cell ◽  
Liposomal Doxorubicin ◽  
Cell Uptake ◽  
Charge Reversal ◽  
Tumor Acidity ◽  
Induced Charge

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

Effects of Chronic  -Adrenergic Receptor Blockade on Peripheral Nerve Conduction, Hypoxic Resistance, Polyols, Na+-K+-ATPase Activity, and Vascular Supply in STZ-D Rats

Diabetes ◽  
1991 ◽  
Vol 40 (12) ◽  
pp. 1652-1658 ◽  
Author(s):  
N. E. Cameron ◽  
M. A. Cotter ◽  
K. Ferguson ◽  
S. Robertson ◽  
M. A. Radcliffe
Keyword(s):  
Peripheral Nerve ◽  
Atpase Activity ◽  
Nerve Conduction ◽  
Adrenergic Receptor ◽  
Vascular Supply ◽  
Receptor Blockade ◽  
Hypoxic Resistance ◽  
Adrenergic Receptor Blockade

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.

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