Bioorthogonal Enzymatic Activation of Caged Compounds

Angew Chem Int Ed Engl. 2015 Nov 2;54(45):13440-3. doi: 10.1002/anie.201506739. Epub 2015 Sep 10.

Abstract

Engineered cytochrome P450 monooxygenase variants are reported as highly active and selective catalysts for the bioorthogonal uncaging of propargylic and benzylic ether protected substrates, including uncaging in living E. coli. observed selectivity is supported by induced-fit docking and molecular dynamics simulations. This proof-of-principle study points towards the utility of bioorthogonal enzyme/protecting group pairs for applications in the life sciences.

Keywords: bioorthogonal chemistry; cytochromes; directed evolution; protecting groups; protein engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemistry
  • Alcohols / metabolism
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism*
  • Enzyme Activation
  • Escherichia coli / cytology
  • Escherichia coli / metabolism*
  • Ethers / chemistry
  • Ethers / metabolism
  • Models, Molecular
  • Molecular Structure
  • Protein Engineering

Substances

  • Alcohols
  • Ethers
  • Cytochrome P-450 Enzyme System