Binding of hydrophobic hydroxamic acids enhances peroxidase's stereoselectivity in nonaqueous sulfoxidations

Prasanta Kumar Das, Jose M.M. Caaveiro, Susana Luque, Alexander M. Klibanov

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Horseradish peroxidase exhibits a meager stereoselectivity (E) in the sulfoxidation of thioanisole (1a) in 99.8% (v/v) methanol. The E value, however, is greatly enhanced when the enzyme forms a complex with benzohydroxamic acid (2a). These findings are rationalized by means of molecular dynamics simulations and energy minimization which correctly explain (i) why the free enzyme is not stereoselective, (ii) why 2a inhibits peroxidase-catalyzed sulfoxidation of 1a but the enzymatic formation of one enantiomer of the sulfoxide product is inhibited much more than that of the other, thereby raising peroxidase's E, and (iii) why in the presence of 2a the enzyme favors production of the S sulfoxide of 1a. The generality of the observed ligand-induced stereoselectivity enhancement is demonstrated with other hydrophobic hydroxamic acids, as well as with additional thioether substrates.

Original languageEnglish
Pages (from-to)782-787
Number of pages6
JournalJournal of the American Chemical Society
Volume124
Issue number5
DOIs
Publication statusPublished - Feb 6 2002
Externally publishedYes

Fingerprint

sulfoxide
Hydroxamic Acids
Stereoselectivity
Enzymes
Acids
Enantiomers
Sulfides
Horseradish Peroxidase
Molecular Dynamics Simulation
Peroxidase
Methanol
Molecular dynamics
Ligands
Computer simulation
Substrates

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Binding of hydrophobic hydroxamic acids enhances peroxidase's stereoselectivity in nonaqueous sulfoxidations. / Das, Prasanta Kumar; Caaveiro, Jose M.M.; Luque, Susana; Klibanov, Alexander M.

In: Journal of the American Chemical Society, Vol. 124, No. 5, 06.02.2002, p. 782-787.

Research output: Contribution to journalArticle

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