Atroposelective antibodies as a designed protein scaffold for artificial metalloenzymes

Sci Rep. 2019 Sep 19;9(1):13551. doi: 10.1038/s41598-019-49844-0.

Abstract

Design and engineering of protein scaffolds are crucial to create artificial metalloenzymes. Herein we report the first example of C-C bond formation catalyzed by artificial metalloenzymes, which consist of monoclonal antibodies (mAbs) and C2 symmetric metal catalysts. Prepared as a tailored protein scaffold for a binaphthyl derivative (BN), mAbs bind metal catalysts bearing a 1,1'-bi-isoquinoline (BIQ) ligand to yield artificial metalloenzymes. These artificial metalloenzymes catalyze the Friedel-Crafts alkylation reaction. In the presence of mAb R44E1, the reaction proceeds with 88% ee. The reaction catalyzed by Cu-catalyst incorporated into the binding site of mAb R44E1 is found to show excellent enantioselectivity with 99% ee. The protein environment also enables the use of BIQ-based catalysts as asymmetric catalysts for the first time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism*
  • Binding Sites
  • Catalysis
  • Cloning, Molecular
  • Copper / metabolism*
  • Isoquinolines / chemistry*
  • Ligands
  • Metalloproteins / chemistry
  • Metalloproteins / metabolism
  • Protein Engineering / methods*

Substances

  • Antibodies, Monoclonal
  • Isoquinolines
  • Ligands
  • Metalloproteins
  • Copper