A number of quaternary ammonium salts with bulky hydrophobic moieties are known to provoke the superactivation of alfa-chymotrypsin (alfa-CT) in aqueous solution. In particular, benzyl-substituted ammonium and dicationic ammonium-based salts have recently emerged as promising classes of compounds to induce a-CT superactivation and stabilization. Preliminary in silico modelling suggested the alfa-CT residue tryptophan 215 to be the major anchor point of these additives. In order to achieve a broader knowledge of the enzyme–additive interactions and to validate the modelling studies, new ammonium- based additives were designed and tested. The hydrophobic interaction resulted in being critical to improving superactivation, with [(2,3,5,6-tetramethyl-p-phenylene)dimethylene]bis[triethylammonium bromide] (bisEDuEAB) resulting as the most effective quaternary ammonium superactivating agent studied so far. Finally, a general agreement between in silico outcomes and kinetic parameters was observed, and data interpretation is discussed based on the proposed alfa-CT/additive binding modes.

Refining the model to design α-chymotrypsin superactivators: the role of the binding mode of quaternary ammonium salts

Gabriele, Francesco;Spreti, Nicoletta
2020

Abstract

A number of quaternary ammonium salts with bulky hydrophobic moieties are known to provoke the superactivation of alfa-chymotrypsin (alfa-CT) in aqueous solution. In particular, benzyl-substituted ammonium and dicationic ammonium-based salts have recently emerged as promising classes of compounds to induce a-CT superactivation and stabilization. Preliminary in silico modelling suggested the alfa-CT residue tryptophan 215 to be the major anchor point of these additives. In order to achieve a broader knowledge of the enzyme–additive interactions and to validate the modelling studies, new ammonium- based additives were designed and tested. The hydrophobic interaction resulted in being critical to improving superactivation, with [(2,3,5,6-tetramethyl-p-phenylene)dimethylene]bis[triethylammonium bromide] (bisEDuEAB) resulting as the most effective quaternary ammonium superactivating agent studied so far. Finally, a general agreement between in silico outcomes and kinetic parameters was observed, and data interpretation is discussed based on the proposed alfa-CT/additive binding modes.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11697/151794
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