title: Structural Dissection of Crotalicidin, a Rattlesnake Venom Cathelicidin, Retrieves a Fragment with Antimicrobial and Antitumor Activity.
abstract: 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.
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra , 08003 Barcelona, Spain.|Laboratory of Biochemistry and Biotechnology, Institute for Marine Sciences, Federal University of Ceará , 60455-760 Fortaleza, CE, Brazil.
authors.forename: Claudio Borges
authors.initials: CB
authors.lastname: Falcao
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra , 08003 Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Pérez-Peinado
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra , 08003 Barcelona, Spain.
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: de la Torre
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques , 08003 Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mayol
authors.affiliation: Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas (CSIC), 28006 Madrid, Spain.
authors.forename: Héctor
authors.initials: H
authors.lastname: Zamora-Carreras
authors.affiliation: Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas (CSIC), 28006 Madrid, Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Jiménez
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra , 08003 Barcelona, Spain.|Laboratory of Biochemistry and Biotechnology, Institute for Marine Sciences, Federal University of Ceará , 60455-760 Fortaleza, CE, Brazil.
authors.forename: Gandhi
authors.initials: G
authors.lastname: Rádis-Baptista
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra , 08003 Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Andreu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003435:Crotalid Venoms / Q000737:chemistry* / Q000494:pharmacology; D017839:Crotalus; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D003435:Crotalid Venoms; D054804:Cathelicidins