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Development of an Enzyme Mimic Using Self‐Selection
Author(s) -
Gasparini Giulio,
Dal Molin Marta,
Corrà Stefano,
Galzerano Patrizia,
Scrimin Paolo,
Prins Leonard J.
Publication year - 2013
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.201200080
Subject(s) - chemistry , substituent , amine gas treating , serine protease , covalent bond , nucleophile , serine , catalysis , combinatorial chemistry , enzyme , enzyme catalysis , protease , stereochemistry , organic chemistry
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.