4-ketoproline: An electrophilic proline analog for bioconjugation

Biopolymers. 2015 Mar;104(2):110-5. doi: 10.1002/bip.22620.


Installing an electrophilic amino-acid residue can engender a peptide or protein with chemoselective reactivity. Such a modification to collagen, which is the most abundant protein in animals, could facilitate the development of new biomaterials. Collagen has an abundance of proline-like residues. Here, we report on the incorporation of an electrophilic proline congener, (2S)-4-ketoproline (Kep), into a collagen-mimetic peptide (CMP). An ab initio conformational analysis of Kep revealed its potential to be accommodated within a collagen triple helix. A synthetic CMP containing a Kep residue was indeed able to form a stable triple helix. Moreover, the condensation of its carbonyl group with aminooxy-biotin did not compromise the conformational stability of the triple helix. These data encourage the use of 4-ketoproline as an electrophilic congener of proline.

Keywords: 4-ketoproline; 4-oxoproline; collagen; host-guest; oxime.

Publication types

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

MeSH terms

  • Collagen / chemistry
  • Peptides / chemistry
  • Proline / analogs & derivatives*
  • Proline / chemistry
  • Protein Conformation


  • Peptides
  • 4-ketoproline
  • Collagen
  • Proline