Butelase 1: A Versatile Ligase for Peptide and Protein Macrocyclization

J Am Chem Soc. 2015 Dec 16;137(49):15398-401. doi: 10.1021/jacs.5b11014. Epub 2015 Dec 7.

Abstract

Macrocyclization is a valuable tool for drug design and protein engineering. Although various methods have been developed to prepare macrocycles, a general and efficient strategy is needed. Here we report a highly efficient method using butelase 1 to macrocyclize peptides and proteins ranging in sizes from 26 to >200 residues. We achieved cyclizations that are 20,000 times faster than sortase A, the most widely used ligase for protein cyclization. The reactions completed within minutes with up to 95% yields.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cyclization
  • Humans
  • Ligases / chemistry
  • Ligases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Synthases / chemistry
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism
  • Peptides / chemistry
  • Peptides / metabolism*
  • Plant Proteins / chemistry
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Proteins / chemistry
  • Proteins / metabolism*
  • Rats

Substances

  • Peptides
  • Plant Proteins
  • Proteins
  • Ligases
  • Peptide Synthases