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

Dastpeyman, Mohadeseh, Bansal, Paramjit S., Wilson, David, Sotillo, Javier, Brindley, Paul J., Loukas, Alex, Smout, Michael J., and Daly, Norelle L. (2018) Structural variants of a liver fluke derived granulin peptide potently stimulate wound healing. Journal of Medicinal Chemistry, 61 (19). pp. 8746-8753.

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Abstract

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.

Item ID: 56065
Item Type: Article (Research - C1)
ISSN: 1520-4804
Copyright Information: Copyright © 2018 American Chemical Society
Funders: James Cook University (JCU), Australian Research Council (ARC), National Health and Medical Research Council (NHMRC), National Cancer Institute, National Institutes of Health (NIH)
Projects and Grants: ARC Future Fellowship Grant 110100226, ARC Grant LE120100015, ARC Grant LE160100218, NHMRC Senior Principal Research Fellowship Grant 1117504, NIH award CA164719
Date Deposited: 07 Nov 2018 09:22
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110899 Medical Microbiology not elsewhere classified @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110199 Medical Biochemistry and Metabolomics not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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