Bioavailable affinity label for collagen prolyl 4-hydroxylase

Bioorg Med Chem. 2013 Jun 15;21(12):3597-601. doi: 10.1016/j.bmc.2013.04.057. Epub 2013 Apr 30.


Collagen is the most abundant protein in animals. Its prevalent 4-hydroxyproline residues contribute greatly to its conformational stability. The hydroxyl groups arise from a post-translational modification catalyzed by the nonheme iron-dependent enzyme, collagen prolyl 4-hydroxylase (P4H). Here, we report that 4-oxo-5,6-epoxyhexanoate, a mimic of the α-ketoglutarate co-substrate, inactivates human P4H. The inactivation installs a ketone functionality in P4H, providing a handle for proteomic experiments. Caenorhabditis elegans exposed to the esterified epoxy ketone displays the phenotype of a worm lacking P4H. Thus, this affinity label can be used to mediate collagen stability in an animal, as is desirable in the treatment of a variety of fibrotic diseases.

Publication types

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

MeSH terms

  • Animals
  • Biocatalysis
  • Collagen / chemistry
  • Collagen / metabolism*
  • Humans
  • Ketones / chemistry
  • Ketones / metabolism
  • Molecular Structure
  • Prolyl Hydroxylases / chemistry
  • Prolyl Hydroxylases / metabolism*


  • Ketones
  • Collagen
  • Prolyl Hydroxylases