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Affinity Labeling
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
Affinity labeling is a technique for the specific modification of an amino acid residue in a protein which involves both the binding of the reagent (affinity label) on the basis of biological specificity and subsequent modification of an amino acid residue through the formation of a covalent bond. There are therefore at least two separate and distinct steps in the process of affinity labeling regardless of whether one is concerned with modification of an enzyme catalytic site or a binding site on a protein not involved in catalysis: the process of specific (selective) binding and the process of covalent bond formation.
Affinity Labeling
Published in Roger L. Lundblad, Claudia M. Noyes, Chemical Reagents for Protein Modification, 1984
Roger L. Lundblad, Claudia M. Noyes
Affinity labeling is a technique for the specific modification of an amino acid residue in a protein which involves both the binding of the reagent (affinity label) on the basis of biological specificity and subsequent modification of an amino acid residue through the formation of a covalent bond. There are therefore at least two separate and distinct steps in the process of affinity labeling regardless of whether one is concerned with modification of an enzyme catalytic site or a binding site on a protein not involved in catalysis: the process of specific (selective) binding and the process of covalent bond formation.
Affinity Labeling
Published in Roger L. Lundblad, Claudia M. Noyes, Chemical Reagents for Protein Modification, 1984
Roger L. Lundblad, Claudia M. Noyes
Affinity labeling is a technique for the specific modification of an amino acid residue in a protein which involves both the binding of the reagent (affinity label) on the basis of biological specificity and subsequent modification of an amino acid residue through the formation of a covalent bond. There are therefore at least two separate and distinct steps in the process of affinity labeling regardless of whether one is concerned with modification of an enzyme catalytic site or a binding site on a protein not involved in catalysis: the process of specific (selective) binding and the process of covalent bond formation.
Approaches to mitigate the risk of serious adverse reactions in covalent drug design
Published in Expert Opinion on Drug Discovery, 2021
As a medicinal chemistry strategy for the discovery of novel therapeutics and probes for chemical biology, the design of enzyme inhibitors that act by a covalent mechanism has received steadily increasing attention over the past decade, as reflected in the rapid growth of publications on various aspects of the topic dating from around 2009. The term ‘targeted covalent inhibitor’ (TCI) was coined by Singh and colleagues [1] to describe this class of agents, and was defined as follows: ‘An inhibitor bearing a bond-forming functional group of low reactivity that, following binding to the target protein, is positioned to react rapidly with a specific non-catalytic residue at the target site.’ Although an expanded classification of covalent inhibitors has been proposed recently, the term TCI will be used in this article to refer to covalent drugs that operate by the ‘classical affinity label’ mechanism described by Tuley and Fast [2].
Inhibition of O-acetylserine sulfhydrylase by fluoroalanine derivatives
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Nina Franko, Konstantinos Grammatoglou, Barbara Campanini, Gabriele Costantino, Aigars Jirgensons, Andrea Mozzarelli
The debate between pros and cons of reversible and irreversible enzyme inhibitors has been developing along the history of medicinal chemistry with alternative views16,17. Reversible inhibitors either directed to the active site or allosteric sites are thought to be more specific, thus less prone to toxicity effects due to unwanted off-target reactions, which are typical of irreversible inhibitors that exploit the intrinsic reactivity of protein residues, such as cysteines or cofactors. However, the concentration of irreversible inhibitors needed to inactivate enzymes is usually lower than the concentration required by reversible inhibitors and this can potentially lead to an increased therapeutic index. Two classes of irreversible inhibitors have been developed: mechanism-based inactivators and affinity labels18,19.