Artificial transaminase carrying a synthetic macrocyclic binding group

Winkler, Jeffrey D.; Coutouli‐Argyropoulou, Evdoxia; Leppkes, R.; Breslow, Ronald

doi:10.1021/ja00362a045

Cited by 53 publications

(13 citation statements)

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“…To investigate if the coenzyme mimics based on pyridoxamine would function with a more general binding group, pyridoxamine was attached to a synthetic macrocycle with a hydrophobic cavity ( 414 , Figure 30). 118c The enzyme model promoted similar substrate selectivities during the competitive transaminations as cyclodextrins 405 and 413 ; however, as 414 is achiral, no chiral induction was observed in the products.…”

Section: Transaminationsmentioning

confidence: 91%

Substrate‐Selective Catalysis

Lindbäck

Dawaigher

Wärnmark

2014

Chemistry A European J

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Substrate selectivity is an important output function for the validation of different enzyme models, catalytic cavity compounds, and reaction mechanisms as demonstrated in this review. In contrast to stereo-, regio-, and chemoselective catalysis, the field of substrate-selective catalysis is under-researched and has to date generated only a few, but important, industrial applications. This review points out the broad spectrum of different reaction types that have been investigated in substrate-selective catalysis. The present review is the first one covering substrate-selective catalysis and deals with reactions in which the substrates involved have the same reacting functionality and the catalysts is used in catalytic or in stoichiometric amounts. The review covers real substrate-selective catalysis, thus only including cases in which substrate-selective catalysis has been observed in competition between substrates.

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Section: Transaminationsmentioning

confidence: 91%

Substrate‐Selective Catalysis

Lindbäck

Dawaigher

Wärnmark

2014

Chemistry A European J

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“…Established kinetic studies on the reaction of pyridoxal and selected amino acids suggested that the [1,3] proton transfer is the rate‐limiting step 39, 40. On account of the unique reactivity of PLP and PMP in biological systems, many attempts have been made to develop biomimetic compounds using these cofactors, particularly for transamination reaction 41–51…”

Section: Introductionmentioning

confidence: 99%

Theoretical studies on pyridoxal 5′‐phosphate‐dependent transamination of α‐amino acids

Liao

Ding

et al. 2008

J Comput Chem

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Density functional methods have been applied to investigate the irreversible transamination between glyoxylic acid and pyridoxamine analog and the catalytic mechanism for the critical [1,3] proton transfer step in aspartate aminotransferase (AATase). The results indicate that the catalytic effect of pyridoxal 5'-phosphate (PLP) may be attributed to its ability to stabilize related transition states through structural resonance. Additionally, the PLP hydroxyl group and the carboxylic group of the amino acid can shuttle proton, thereby lowering the barrier. The rate-limiting step is the tautomeric conversion of the aldimine to ketimine by [1,3] proton transfer, with a barrier of 36.3 kcal/mol in water solvent. A quantum chemical model consisting 142 atoms was constructed based on the crystal structure of the native AATase complex with the product L-glutamate. The electron-withdrawing stabilization by various residues, involving Arg386, Tyr225, Asp222, Asn194, and peptide backbone, enhances the carbon acidity of 4'-C of PLP and Calpha of amino acid. The calculations support the proposed proton transfer mechanism in which Lys258 acts as a base to shuttle a proton from the 4'-C of PLP to Calpha of amino acid. The first step (proton transfer from 4'-C to lysine) is shown to be the rate-limiting step. Furthermore, we provided an explanation for the reversibility and specificity of the transamination in AATase.

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“…The laser flash photolysis apparatus has been described previously. 16 All reactions were carried out under a N2 or Ar atmosphere and at ambient temperature (20-24 °C).…”

Section: Methodsmentioning

confidence: 99%