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Publication Abstract from PubMed

Granulins are a family of protein growth factors that are involved in cell proliferation. An orthologue of granulin from the human parasitic liver fluke Opisthorchis viverrini, known as Ov-GRN-1, induces angiogenesis and accelerates wound repair. Recombinant Ov-GRN-1 production is complex and poses an obstacle for clinical development. To identify the bioactive region(s) of Ov-GRN-1, four truncated N-terminal analogues were synthesized and characterized structurally using NMR spectroscopy. Peptides that contained only two native disulfide bonds lack the characteristic granulin beta-hairpin structure. Remarkably, the introduction of a non-native disulfide bond was critical for formation of beta-hairpin structure. Despite this structural difference, both two and three disulfide-bonded peptides drove proliferation of a human cholangiocyte cell line and demonstrated potent wound healing in mice. Peptides derived from Ov-GRN-1 are leads for novel wound healing therapeutics, as they are likely less immunogenic than the full-length protein and more convenient to produce.

Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold.,Bansal PS, Smout MJ, Wilson D, Cobos Caceres C, Dastpeyman M, Sotillo J, Seifert J, Brindley PJ, Loukas A, Daly NL J Med Chem. 2017 May 25;60(10):4258-4266. doi: 10.1021/acs.jmedchem.7b00047. Epub, 2017 May 3. PMID:28425707^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.