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Título: | Structural Dissection of Crotalicidin, a Rattlesnake Venom Cathelicidin, Retrieves a Fragment with Antimicrobial and Antitumor Activity |
Autor: | Falcao, C.B.; Pérez-Peinado, C.; De La Torre, B.G.; Mayol, X.; Zamora-Carreras, H.; Jiménez, M. Angeles CSIC ORCID ; Rádis-Baptista, G.; Andreu, D. | Fecha de publicación: | 2015 | Citación: | Journal of Medicinal Chemistry 58: 8553- 8563 (2015) | Resumen: | In silico dissection of crotalicidin (Ctn), a cathelicidin from a South American pit viper, yielded fragments Ctn[1-14] and Ctn[15-34], which were tested to ascertain to what extent they reproduced the structure and activity of the parent peptide. NMR data showing Ctn to be α-helical at the N-terminus and unstructured at the C-terminus were matched by similar data from the fragments. The peptides were tested against Gram-positive and -negative bacteria and for toxicity against both tumor and healthy cells. Despite its amphipathic α-helical structure, Ctn[1-14] was totally inert toward bacteria or eukaryotic cells. In contrast, unstructured Ctn[15-34] replicated the activity of parent Ctn against Gram-negative bacteria and tumor cells while being significantly less toxic toward eukaryotic cells. This selectivity for bacteria and tumor cells, plus a stability to serum well above that of Ctn, portrays Ctn[15-34] as an appealing candidate for further development as an anti-infective or antitumor lead. | URI: | http://hdl.handle.net/10261/141985 | DOI: | 10.1021/acs.jmedchem.5b01142 | Identificadores: | doi: 10.1021/acs.jmedchem.5b01142 issn: 1520-4804 |
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