Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 60, Issue 10, Pages 4258-4266Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.7b00047
Keywords
-
Categories
Funding
- R01 grant from the National Cancer Institute, USA [R01CA164719]
- National Health and Medical Research Council, Australia (NHMRC) [1037304]
- NHMRC [1020114]
- Australian Research Council [FF110100226]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available