Structural variants of a liver fluke derived granulin peptide potently stimulate wound healing

Dastpeyman M1, Bansal PS1, Wilson D1, Sotillo J1, Brindley PJ2, Loukas A1, Smout MJ1 and Daly NL1

  1. James Cook University, Cairns Australia.
  2. George Washington University, Washington USA.

Granulins are a family of growth factors involved in cell proliferation. The liver-fluke granulin, Ov-GRN-1, isolated from a carcinogenic liver fluke Opisthorchis viverrini, can significantly accelerate wound repair in vivo and in vitro. However, it is difficult to express Ov-GRN-1 in recombinant form at high yield, impeding its utility as a drug lead. A truncated analogue (Ov-GRN12-35_3s) promotes healing of cutaneous wounds in mice. NMR analysis of this analogue indicates the presence of multiple conformations, most likely as a result of proline cis/trans isomerisation. To further investigate whether the proline residues are involved in adopting the multiple confirmations we have synthesised analogues involving mutation of the proline residues. We have shown that the proline residues have a significant influence on the structure, activity and folding of Ov-GRN12-35_3s. These results provide insight into improving the oxidative folding yield and bioactivity of Ov-GRN12-35_3s, and might facilitate the development of a novel wound healing agent.