Three-in-one chromatography-free purification, tag removal, and site-specific modification of recombinant fusion proteins using sortase A and elastin-like polypeptides

Angew Chem Int Ed Engl. 2013 Mar 25;52(13):3703-8. doi: 10.1002/anie.201208292. Epub 2013 Feb 19.

Abstract

Applied in tandem, elastin-like polypeptides (ELPs) and the sortase A (SrtA) transpeptidase from Staphylococcus aureus provide a general method for chromatography-free purification of tag-free recombinant proteins and optional, site-specific and homogeneous conjugation of the protein to a small molecule. This system provides an efficient, practical mechanism for generating bioactive proteins and protein-small-molecule combination therapeutics at high yields and purities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoacyltransferases / genetics
  • Aminoacyltransferases / metabolism*
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / toxicity
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Elastin / genetics
  • Elastin / metabolism*
  • Escherichia coli / metabolism
  • Humans
  • Mice
  • Mutagenesis, Site-Directed
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Staphylococcus aureus / enzymology
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antineoplastic Agents
  • Bacterial Proteins
  • Recombinant Fusion Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha
  • Elastin
  • Aminoacyltransferases
  • sortase A
  • Cysteine Endopeptidases