The development of a serine protease model using a self-selection protocol is described. The developed system mimics the regeneration step of an enzyme involved in covalent enzyme catalysis. A transition-state analogue of a transesterification reaction is used to self-select functional groups able to accelerate ester cleavage. It is shown that the insertion of a tertiary amine substituent flanking the reaction center reinforces transition-state stabilization by directing the reactive center towards the self-selected functionality. In addition, the tertiary amine activates a bland (solvent) nucleophile for attack on an ester bond similar to what occurs in a serine protease. A quantitative correspondence is observed between the amplification factors and catalytic activity, illustrating the potential of the dynamic covalent capture strategy to precisely detect and quantify weak noncovalent interactions. © 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Gasparini G., Dal Molin M., Stefano Corra, Galzerano P., Scrimin P., Prins L.J. (2013). Development of an enzyme mimic using self-selection. ISRAEL JOURNAL OF CHEMISTRY, 53(1-2), 122-126 [10.1002/ijch.201200080].
Development of an enzyme mimic using self-selection
Stefano Corra;Galzerano P.;
2013
Abstract
The development of a serine protease model using a self-selection protocol is described. The developed system mimics the regeneration step of an enzyme involved in covalent enzyme catalysis. A transition-state analogue of a transesterification reaction is used to self-select functional groups able to accelerate ester cleavage. It is shown that the insertion of a tertiary amine substituent flanking the reaction center reinforces transition-state stabilization by directing the reactive center towards the self-selected functionality. In addition, the tertiary amine activates a bland (solvent) nucleophile for attack on an ester bond similar to what occurs in a serine protease. A quantitative correspondence is observed between the amplification factors and catalytic activity, illustrating the potential of the dynamic covalent capture strategy to precisely detect and quantify weak noncovalent interactions. © 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.