Structural Variants of a Liver Fluke Derived Granulin Peptide Potently Stimulate Wound Healing

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. Previously
we reported that 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 isomerization. To further investigate whether the proline residues
are involved in adopting the multiple confirmations, we have synthesized
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.