0576497 - BC 2024 RIV US eng J - Journal Article
Chai, J. - Wu, J. - Li, J. - Liao, H. - Lu, W. - Guo, R. - Shao, Z. - Jmel, Mohamed Amine - Martins, Larissa Almeida - Hackeng, T. - Ippel, H. - Dijkgraaf, I. - Kotsyfakis, Michalis - Xu, X.
Novel Amphibian Bowman-Birk-Like Inhibitor with Antioxidant and Anticoagulant Effects Ameliorates Pancreatitis Symptoms in Mice.
Journal of Medicinal Chemistry. Roč. 66, č. 17 (2023), s. 11869-11880. ISSN 0022-2623. E-ISSN 1520-4804
Grant - others:AV ČR(CZ) NSFC-19-15
Program: Bilaterální spolupráce
Institutional support: RVO:60077344
Keywords : PEPTIDE LEUCINE ARGININE * TRYPSIN-INHIBITOR * SKIN SECRETIONS
OECD category: Pharmacology and pharmacy
Impact factor: 6.8, year: 2023
Method of publishing: Limited access
https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00475

Acute pancreatitis (AP) is a serious inflammatory disorder and still lacks effective therapy globally. In this study, a novel Ranacyclin peptide, Ranacin, was identified from the skin of Pelophylax nigromaculatus frog. Ranacin adopted a compact ss hairpin conformation with a disulfide bond (Cys5-Cys15). Ranacin was also demonstrated effectively to inhibit trypsin and have anticoagulant and antioxidant activities in vitro. Furthermore, the severity of pancreatitis was significantly alleviated in L-Arg-induced AP mice after treatment with Ranacin. In addition, structure-activity studies of Ranacin analogues confirmed that the sequences outside the trypsin inhibitory loop (TIL), especially at the C-terminal side, might be closely associated with the efficacy of its trypsin inhibitory activity. In conclusion, our data suggest that Ranacin can improve pancreatic injury in mice with severe AP through its multi-activity. Therefore, Ranacin is considered a potential drug candidate in AP therapy.
Permanent Link: https://hdl.handle.net/11104/0346051