Biotecnología Aplicada ()

Rational design of an antitumor peptide based on the 32-51 region of the Limulus anti-LPS factor protein obtained from a chemical library

  • Maribel Guerra-Vallespi,
  • Julio R Fernández-Massó,
  • Osvaldo Reyes-Acosta,
  • Hilda Garay-Pérez,
  • Isis Torrens-Madrazo,
  • Milaid Granadillo-Rodríguez,
  • Brizaida Oliva-Argüelles,
  • Isbel García,
  • Isabel Guillén-Pérez,
  • Daniel Palenzuela-Gardón,
  • Dania Vázquez-Blomquist,
  • Viviana Falcón-Cama,
  • Osmany Mendoza-Fuentes,
  • Orlando Borras-Hidalgo,
  • Lidia I Novoa-Pérez,
  • Mariela Vázquez-Castillo

Journal volume & issue
Vol. 31, no. 4
pp. 328 – 331

Abstract

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In previous work, we identified the peptide comprising amino acids 32-51 on the antimicrobial protein limulus anti-LPS factor (LALF) from Limulus poliphemus, based on its capacity to bind to the bacterial lipopolysaccharide (LPS). In this study, we designed a chemical peptide library by alanine scanning from the sequence of the LALF32-51 peptide. Four new peptides, named L-2, L-8, L-12 and L-20 by the Ala residue substituted in the given position of the LALF32-51 peptide, were identified as retaining their penetrating activity but also showing antitumor effects when subcutaneously administered in female C57Bl/6 mice after the implantation of malignant TC-1 lung epithelial cells. They significantly increased animal survival (p < 0.05) as compared to LALF32-51. The substitution of Tyr residue to Ala at position 2 in the peptide sequence enhanced the cytotoxic effect, while residues Phe8, Lys12 and Trp20 were essential for the antitumor activity. Moreover, the administration of the L-2 peptide significantly reduced tumor growth in comparison to PBS- or L-20 peptide-treated lung TC-1 cells in C57Bl/6 mice. L-2 was found to deregulate the tumor cell cycle and induces apoptosis, through mechanisms affecting glycolytic and protein biosynthesis pathways. It also significantly increased survival in human colon cancer LS-174T xenotransplanted nude mice for up to 32 days, two of the animals being tumor free. The L-2 peptide could serve as peptide-based prototype drug with potential to reduce tumor load or could be coadministered with conventional chemotherapy. This research granted the 2013 Award of the Cuban National Academy of Sciences.

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