| Autor: |
Dastpeyman M; Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine , James Cook University , Cairns , QLD 4870 , Australia., Bansal PS; Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine , James Cook University , Cairns , QLD 4870 , Australia., Wilson D; Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine , James Cook University , Cairns , QLD 4870 , Australia., Sotillo J; Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine , James Cook University , Cairns , QLD 4870 , Australia., Brindley PJ; Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences , George Washington University , Washington, D.C. 20052 , United States., Loukas A; Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine , James Cook University , Cairns , QLD 4870 , Australia., Smout MJ; Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine , James Cook University , Cairns , QLD 4870 , Australia., Daly NL; Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine , James Cook University , Cairns , QLD 4870 , Australia. |
| Abstrakt: |
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-GRN 12-35_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-GRN 12-35_3s . These results provide insight into improving the oxidative folding yield and bioactivity of Ov-GRN 12-35_3s and might facilitate the development of a novel wound healing agent. |
