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Novel Amphibian Bowman-Birk-Like Inhibitor with Antioxidant and Anticoagulant Effects Ameliorates Pancreatitis Symptoms in Mice
- 1.
SYSNO ASEP 0576497 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Novel Amphibian Bowman-Birk-Like Inhibitor with Antioxidant and Anticoagulant Effects Ameliorates Pancreatitis Symptoms in Mice Tvůrce(i) Chai, J. (CN)
Wu, J. (CN)
Li, J. (CN)
Liao, H. (CN)
Lu, W. (CN)
Guo, R. (CN)
Shao, Z. (CN)
Jmel, Mohamed Amine (BC-A) RID, ORCID
Martins, Larissa Almeida (BC-A) RID, ORCID
Hackeng, T. (NL)
Ippel, H. (NL)
Dijkgraaf, I. (NL)
Kotsyfakis, Michalis (BC-A) RID, ORCID
Xu, X. (CN)Celkový počet autorů 14 Zdroj.dok. Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623
Roč. 66, č. 17 (2023), s. 11869-11880Poč.str. 12 s. Forma vydání Tištěná - P Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova PEPTIDE LEUCINE ARGININE ; TRYPSIN-INHIBITOR ; SKIN SECRETIONS Vědní obor RIV FR - Farmakologie a lékárnická chemie Obor OECD Pharmacology and pharmacy Způsob publikování Omezený přístup Institucionální podpora BC-A - RVO:60077344 UT WOS 001063451900001 EID SCOPUS 85169893281 DOI https://doi.org/10.1021/acs.jmedchem.3c00475 Anotace 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. Pracoviště Biologické centrum (od r. 2006) Kontakt Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Rok sběru 2024 Elektronická adresa https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00475
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