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IsCT-based analogs intending better biological activity.
Acevedo, Isabel Cristina Chica; Silva, Pedro Ismael; Silva, Fernanda Dias; Araújo, Iris; Alves, Flávio Lopes; Oliveira, Cyntia Silva; Oliveira, Vani Xavier.
Afiliación
  • Acevedo ICC; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
  • Silva PI; Laboratório Especial de Toxinologia Aplicada, Instituto Butantan, São Paulo, SP, Brazil.
  • Silva FD; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
  • Araújo I; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
  • Alves FL; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
  • Oliveira CS; Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
  • Oliveira VX; Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
J Pept Sci ; 25(12): e3219, 2019 Dec.
Article en En | MEDLINE | ID: mdl-31642159
IsCT1-NH2 is a cationic antimicrobial peptide isolated from the venom of the scorpion Opisthacanthus madagascariensis that has a tendency to form an α-helical structure and shows potent antimicrobial activity and also inopportunely shows hemolytic effects. In this study, five IsCT1 (ILGKIWEGIKSLF)-based analogs with amino acid modifications at positions 1, 3, 5, or 8 and one analog with three simultaneous substitutions at the 1, 5, and 8 positions were designed. The net charge of each analog was between +2 and +3. The peptides obtained were characterized by mass spectrometry and analyzed by circular dichroism for their structure in different media. Studies of antimicrobial activity, hemolytic activity, and stability against proteases were also carried out. Peptides with a substitution at position 3 or 5 ([L]3 -IsCT1-NH2 , [K]3 -IsCT1-NH2 , or [F]5 -IsCT1-NH2 ) showed no significant change in an activity relative to IsCT1-NH2 . The addition of a proline residue at position 8 ([P]8 -IsCT1-NH2 ) reduced the hemolytic activity as well as the antimicrobial activity (MIC ranging 3.13-50 µmol L-1 ), and the addition of a tryptophan residue at position 1 ([W]1 -IsCT1-NH2 ) increased the hemolytic activity (MHC = 1.56 µmol L-1 ) without an improvement in antimicrobial activity. The analog [A]1 [F]5 [K]8 -IsCT1-NH2 , which carries three simultaneous modifications, presented increasing or equivalent values in antimicrobial activity (MIC approximately 0.38 and 12.5 µmol L-1 ) with a reduction in hemolytic activity. In addition, this analog presented the best resistance against proteases. This kind of strategy can find functional hotspots in peptide molecules in an attempt to generate novel potent peptide antibiotics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Proteasas / Venenos de Escorpión / Péptidos Catiónicos Antimicrobianos / Bacterias Gramnegativas / Bacterias Grampositivas / Antibacterianos Límite: Animals Idioma: En Revista: J Pept Sci Asunto de la revista: BIOQUIMICA Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Proteasas / Venenos de Escorpión / Péptidos Catiónicos Antimicrobianos / Bacterias Gramnegativas / Bacterias Grampositivas / Antibacterianos Límite: Animals Idioma: En Revista: J Pept Sci Asunto de la revista: BIOQUIMICA Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido