Ranacyclin-NF, a Novel Bowman–Birk Type Protease Inhibitor from the Skin Secretion of the East Asian Frog, Pelophylax nigromaculatus
| Autor: | Mei Zhou, Chengbang Ma, Xiaoling Chen, Tianbao Chen, Yingqi Zhang, Christopher Shaw, Tao Wang, Yangyang Jiang, Xinping Xi, Lei Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
trypsin inhibitor Odorrana grahami structure–activity relationship Trypsin inhibitor Peptide Biology medicine.disease_cause ranacyclin General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Bowman–Birk inhibitor synergistic effect medicine Structure–activity relationship Secretion Gentamicin lcsh:QH301-705.5 chemistry.chemical_classification General Immunology and Microbiology Trypsin biology.organism_classification Molecular biology Protease inhibitor (biology) 030104 developmental biology chemistry lcsh:Biology (General) Staphylococcus aureus 030220 oncology & carcinogenesis General Agricultural and Biological Sciences medicine.drug |
| Zdroj: | Biology, Vol 9, Iss 149, p 149 (2020) Wang, T, Jiang, Y, Chen, X, Wang, L, Ma, C, Xi, X, Zhang, Y, Chen, T, Shaw, C & Zhou, M 2020, ' Ranacyclin-NF, a Novel Bowman–Birk Type Protease Inhibitor from the Skin Secretion of the East Asian Frog, Pelophylax nigromaculatus ', Biology, vol. 9, no. 7, 149 . https://doi.org/10.3390/biology9070149 Biology Volume 9 Issue 7 |
| ISSN: | 2079-7737 |
| DOI: | 10.3390/biology9070149 |
| Popis: | Serine protease inhibitors are found in plants, animals and microorganisms, where they play important roles in many physiological and pathological processes. Inhibitor scaffolds based on natural proteins and peptides have gradually become the focus of current research as they tend to bind to their targets with greater specificity than small molecules. In this report, a novel Bowman&ndash Birk type inhibitor, named ranacyclin-NF (RNF), is described and was identified in the skin secretion of the East Asian frog, Pelophylax nigromaculatus. A synthetic replicate of the peptide was subjected to a series of functional assays. It displayed trypsin inhibitory activity with an inhibitory constant, Ki, of 447 nM and had negligible direct cytotoxicity. No observable direct antimicrobial activity was found but RNF improved the therapeutic potency of Gentamicin against Methicillin-resistant Staphylococcus aureus (MRSA). RNF shared significant sequence similarity to previously reported and related inhibitors from Odorrana grahami (ORB) and Rana esculenta (ranacyclin-T), both of which were found to be multi-functional. Two analogues of RNF, named ranacyclin-NF1 (RNF1) and ranacyclin-NF3L (RNF3L), were designed based on some features of ORB and ranacyclin-T to study structure&ndash activity relationships. Structure&ndash activity studies demonstrated that residues outside of the trypsin inhibitory loop (TIL) may be related to the efficacy of trypsin inhibitory activity. |
| Databáze: | OpenAIRE |
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