4-ketoproline: An electrophilic proline analog for bioconjugation

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.