Versatile C(3)-symmetric scaffolds and their use for covalent stabilization of the foldon trimer

Org Biomol Chem. 2014 Apr 28;12(16):2606-14. doi: 10.1039/c3ob42251h.


C3-Symmetric trimesic acid scaffolds, functionalized with bromoacetyl, aminooxyacetyl and azidoacetyl moieties, respectively, were synthesized and compared regarding their utility for the trivalent presentation of peptides using three different chemoselective ligation reactions, i.e. thioether and oxime formation, as well as the "click" reaction. The latter ligation method was then used to covalently stabilize the trimer of foldon, a 27 amino acid trimerization domain of bacteriophage T4 fibritin, by linking the three foldon monomers to the triazido-functionalized trimesic acid scaffold. This reaction dramatically enhanced the thermal stability of the trimer, while maintaining the correct fold, as demonstrated by CD spectroscopy and X-ray crystal structure analysis, respectively, of the foldon-scaffold conjugates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriophage T4 / chemistry
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Structure
  • Protein Folding
  • Tricarboxylic Acids / chemical synthesis*
  • Tricarboxylic Acids / chemistry*
  • Viral Proteins / chemistry*


  • Tricarboxylic Acids
  • Viral Proteins
  • fibritin protein, Enterobacteria phage T4
  • trimesic acid