CHAPTER 3. Reversible Covalent Bond Formation as a Strategy for Healable Polymer Networks

Electrophilic natural products have provided fertile ground for understanding how nature inhibits protein function using covalent bond formation. The fungal strain Gymnascella dankaliensis has provided an especially interesting collection of...

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Material Adhesion through Direct Covalent Bond Formation Assisted by Noncovalent Interactions

ACS Applied Polymer Materials ◽

10.1021/acsapm.1c00223 ◽

2021 ◽

Author(s):

Motofumi Osaki ◽

Tomoko Sekine ◽

Hiroyasu Yamaguchi ◽

Yoshinori Takashima ◽

Akira Harada

Keyword(s):

Noncovalent Interactions ◽

Bond Formation ◽

Covalent Bond ◽

Covalent Bond Formation

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Molecular recognition of organic ammonium ions in solution using synthetic receptors

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.6.32 ◽

2010 ◽

Vol 6 ◽

Cited By ~ 145

Author(s):

Andreas Späth ◽

Burkhard König

Keyword(s):

Molecular Recognition ◽

Hydrophobic Interactions ◽

Covalent Bond ◽

Ammonium Ion ◽

Synthetic Receptors ◽

Ammonium Ions ◽

Wide Range ◽

Covalent Bond Formation ◽

Reversible Covalent ◽

Ion Receptors

Ammonium ions are ubiquitous in chemistry and molecular biology. Considerable efforts have been undertaken to develop synthetic receptors for their selective molecular recognition. The type of host compounds for organic ammonium ion binding span a wide range from crown ethers to calixarenes to metal complexes. Typical intermolecular interactions are hydrogen bonds, electrostatic and cation–π interactions, hydrophobic interactions or reversible covalent bond formation. In this review we discuss the different classes of synthetic receptors for organic ammonium ion recognition and illustrate the scope and limitations of each class with selected examples from the recent literature. The molecular recognition of ammonium ions in amino acids is included and the enantioselective binding of chiral ammonium ions by synthetic receptors is also covered. In our conclusion we compare the strengths and weaknesses of the different types of ammonium ion receptors which may help to select the best approach for specific applications.

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Mechanism of Covalent Binding of Ibrutinib to Bruton’s Tyrosine Kinase revealed by QM/MM Calculations

10.26434/chemrxiv.13149893 ◽

2020 ◽

Author(s):

Angus Voice ◽

Gary Tresadern ◽

Rebecca Twidale ◽

Herman Van Vlijmen ◽

Adrian Mulholland

Keyword(s):

Tyrosine Kinase ◽

Covalent Binding ◽

Bond Formation ◽

Covalent Bond ◽

Covalent Modification ◽

Mechanistic Study ◽

Bruton’S Tyrosine Kinase ◽

Bruton's Tyrosine Kinase ◽

Covalent Inhibitors ◽

Covalent Bond Formation

Ibrutinib is the first covalent inhibitor of Bruton’s tyrosine kinase (BTK) to be used in the treatment of B-cell cancers. Understanding the mechanism of covalent inhibition is crucial for the design of safer and more selective covalent inhibitors that target BTK. There are questions surrounding the precise mechanism of covalent bond formation in BTK as there is no appropriate active site residue that can act as a base to deprotonate the cysteine thiol prior to covalent bond formation. To address this, we have investigated several mechanistic pathways of covalent modification of C481 in BTK by ibrutinib using QM/MM reaction simulations. The lowest energy pathway we identified involves a direct proton transfer from C481 to the acrylamide warhead in ibrutinib, followed by covalent bond formation to form an enol intermediate. There is a subsequent rate-limiting keto-enol tautomerisation step (DG‡=10.5 kcal mol-1) to reach the inactivated BTK/ibrutinib complex. Our results represent the first mechanistic study of BTK inactivation by ibrutinib to consider multiple mechanistic pathways. These findings should aid in the design of covalent drugs that target BTK and related proteins.

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Supramolecular Assembly-Enabled Homochiral Polymerization of Short (dA)n Oligonucleotides

Chemical Communications ◽

10.1039/d1cc05420a ◽

2021 ◽

Author(s):

Sreejith Mangalath ◽

Suneesh C Karunakaran ◽

Gary Newnam ◽

Gary Schuster ◽

Nicholas Hud

Keyword(s):

Supramolecular Chemistry ◽

Bond Formation ◽

Supramolecular Assembly ◽

Covalent Bond ◽

Complex Mixtures ◽

Covalent Bond Formation

A goal of supramolecular chemistry is to create covalent polymers of precise composition and stereochemistry from complex mixtures by the reversible assembly of specific monomers prior to covalent bond formation....

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