Thiol-click chemistry: a multifaceted toolbox for small molecule and polymer synthesis

2010 ◽  
Vol 39 (4) ◽  
pp. 1355 ◽  
Author(s):  
Charles E. Hoyle ◽  
Andrew B. Lowe ◽  
Christopher N. Bowman
Keyword(s):  
Click Chemistry ◽  
Small Molecule ◽  
Polymer Synthesis

ChemInform Abstract: Thiol-Click Chemistry: A Multifaceted Toolbox for Small Molecule and Polymer Synthesis

ChemInform ◽  
2010 ◽  
Vol 41 (28) ◽  
pp. no-no
Author(s):  
Charles E. Hoyle ◽  
Andrew B. Lowe ◽  
Christopher N. Bowman
Keyword(s):  
Click Chemistry ◽  
Small Molecule ◽  
Polymer Synthesis

scholarly journals Aqueous synthesis of a small-molecule lanthanide chelator amenable to copper-free click chemistry

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0209726 ◽  
Author(s):  
Stephanie C. Bishop ◽  
Robert Winefield ◽  
Asokan Anbanandam ◽  
Jed N. Lampe
Keyword(s):  
Click Chemistry ◽  
Small Molecule ◽  
Aqueous Synthesis

scholarly journals Development of solvent-free synthesis of hydrogen-bonded supramolecular polyurethanes

2015 ◽  
Vol 6 (4) ◽  
pp. 2382-2388 ◽  
Author(s):  
Kelly. A. Houton ◽  
George M. Burslem ◽  
Andrew. J. Wilson
Keyword(s):  
Ball Milling ◽  
Small Molecule ◽  
Polymer Synthesis ◽  
Solvent Free ◽  
Supramolecular Polymer ◽  
Milling Method ◽  
Solvent Free Synthesis ◽  
Hydrogen Bonded

A solvent free ball-milling method for the synthesis of small molecule and oligomeric carbamates is described that is applicable to supramolecular polymer synthesis.

scholarly journals Aqueous synthesis of a small-molecule lanthanide chelator amenable to copper-free click chemistry

2019 ◽  
Author(s):  
Stephanie Cara Bishop ◽  
Robert Winefield ◽  
Asokan Anbanandam ◽  
Jed Noah Lampe
Keyword(s):  
Click Chemistry ◽  
Small Molecule ◽  
Unnatural Amino Acids ◽  
Protein Denaturation ◽  
Copper Catalyst ◽  
Chelating Agent ◽  
Unnatural Amino Acid ◽  
Aqueous Synthesis ◽  
Site Specific ◽  
Biophysical Studies

The lanthanides (Ln3+), or rare earth elements, have proven to be useful tools for biomolecular NMR, X-ray crystallographic, and fluorescence analyses due to their unique 4f orbitals. However, their utility in biological applications has been limited because site-specific incorporation of a chelating element is required to ensure efficient binding of the free Ln3+ ion. Additionally, current Ln3+ chelator syntheses complicate efforts to directly incorporate Ln3+ chelators into proteins as the multi-step processes and a reliance on organic solvents promote protein denaturation and aggregation which are generally incompatible with direct incorporation into the protein of interest. To overcome these limitations, herein we describe a two-step aqueous synthesis of a small molecule lanthanide chelating agent amenable to site-specific incorporation into a protein using copper-free click chemistry with unnatural amino acids. The bioconjugate combines a diethylenetriaminepentaacetic acid (DTPA) chelating moiety with a clickable dibenzylcyclooctyne-amine (DBCO-amine) to facilitate the reaction with an azide containing unnatural amino acid. Incorporating the DBCO-amine avoids the use of the cytotoxic Cu2+ ion as a catalyst. The clickable lanthanide chelator (CLC) reagent reacted readily with p-azidophenylalanine (paF) without the need of a copper catalyst, thereby demonstrating proof-of-concept. Implementation of the orthogonal click chemistry reaction has the added advantage that the chelator can be used directly in a protein labeling reaction, without the need of extensive purification. Given the inherent advantages of Cu2+-free click chemistry, aqueous synthesis, and facile labeling, we believe that the CLC will find abundant use in both structural and biophysical studies of proteins and their complexes.

SuFEx-Enabled High-Throughput Medicinal Chemistry

2019 ◽  
Author(s):  
Seiya Kitamura ◽  
Qinheng Zheng ◽  
Jordan L. Woehl ◽  
angelo solan ◽  
Emily Chen ◽  
...  
Keyword(s):  
Click Chemistry ◽  
Small Molecule ◽  
High Throughput ◽  
Cysteine Protease ◽  
High Throughput Screening ◽  
Medicinal Chemistry ◽  
Biologically Active ◽  
Drug Candidates ◽  
Biological Probes ◽  
Small Molecule Probes

<p>Optimization of small-molecule probes or drugs is a lengthy, challenging and resource-intensive process. Lack of automation and reliance on skilled medicinal chemists is cumbersome in both academic and industrial settings. Here, we demonstrate a high-throughput hit-to-lead process based on the biocompatible SuFEx click chemistry. A modest high-throughput screening hit against a bacterial cysteine protease SpeB was modified with a SuFExable iminosulfur oxydifluoride [RN=S(O)F2] motif, rapidly diversified into 460 analogs in overnight reactions, and the products directly screened to yield drug-like inhibitors with 300-fold higher potency. We showed that the improved molecule is drug-like and biologically active in a bacteria-host coculture. Since these reactions can be performed on a picomole scale to conserve reagents, we anticipate our methodology can accelerate the development of robust biological probes and drug candidates.</p>

Design and Synthesis of a New, Conformationally Constrained, Macrocyclic Small-Molecule Inhibitor of STAT3 via “Click Chemistry”.

ChemInform ◽  
2007 ◽  
Vol 38 (45) ◽  
Author(s):  
Jianyong Chen ◽  
Zaneta Nikolovska-Coleska ◽  
Chao-Yie Yang ◽  
Cindy Gomez ◽  
Wei Gao ◽  
...  
Keyword(s):  
Click Chemistry ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Conformationally Constrained ◽  
Design And Synthesis ◽  
Molecule Inhibitor

Target validation using in-cell small molecule clickable imaging probes

MedChemComm ◽  
2014 ◽  
Vol 5 (3) ◽  
pp. 247-254 ◽  
Author(s):  
Brahma Ghosh ◽  
Lyn H. Jones
Keyword(s):  
Click Chemistry ◽  
Small Molecule ◽  
Mode Of Action ◽  
Chemical Biology ◽  
Target Validation ◽  
Chemical Probes ◽  
Imaging Probes ◽  
Molecular Mode

The application of click chemistry to the visualization of chemical probes in in-cell chemical biology experiments is reviewed and the influence this research has had on target validation and molecular mode of action studies is also highlighted.

SuFEx-Enabled High-Throughput Medicinal Chemistry

2019 ◽  
Author(s):  
Seiya Kitamura ◽  
Qinheng Zheng ◽  
Jordan L. Woehl ◽  
angelo solan ◽  
Emily Chen ◽  
...  
Keyword(s):  
Click Chemistry ◽  
Small Molecule ◽  
High Throughput ◽  
Cysteine Protease ◽  
High Throughput Screening ◽  
Medicinal Chemistry ◽  
Biologically Active ◽  
Drug Candidates ◽  
Biological Probes ◽  
Small Molecule Probes

<p>Optimization of small-molecule probes or drugs is a lengthy, challenging and resource-intensive process. Lack of automation and reliance on skilled medicinal chemists is cumbersome in both academic and industrial settings. Here, we demonstrate a high-throughput hit-to-lead process based on the biocompatible SuFEx click chemistry. A modest high-throughput screening hit against a bacterial cysteine protease SpeB was modified with a SuFExable iminosulfur oxydifluoride [RN=S(O)F2] motif, rapidly diversified into 460 analogs in overnight reactions, and the products directly screened to yield drug-like inhibitors with 300-fold higher potency. We showed that the improved molecule is drug-like and biologically active in a bacteria-host coculture. Since these reactions can be performed on a picomole scale to conserve reagents, we anticipate our methodology can accelerate the development of robust biological probes and drug candidates.</p>

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