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Computational study, synthesis and evaluation of active peptides derived from Parasporin-2 and spike protein from Alphacoronavirus against colorectal cancer cells.
Cruz, Jenniffer; Suárez-Barrera, Miguel Orlando; Rondón-Villarreal, Paola; Olarte-Diaz, Andrés; Guzmán, Fanny; Visser, Lydia; Rueda-Forero, Nohora Juliana.
  • Cruz J; Universidad de Santander, Facultad de Ciencias Médicas y de la Salud, Instituto de Investigación Masira, Bucaramanga, Colombia.
  • Suárez-Barrera MO; Universidad de Santander, Facultad de Ciencias Médicas y de la Salud, Instituto de Investigación Masira, Bucaramanga, Colombia.
  • Rondón-Villarreal P; Department of Pathology and Medical Biology, University of Groningen, University medical Center Groningen, Groningen, Netherlands.
  • Olarte-Diaz A; Corporación Académica Ciencias Básicas Biomédicas Universidad de Antioquia, Medellín, Colombia.
  • Guzmán F; Universidad de Santander, Facultad de Ciencias Médicas y de la Salud, Instituto de Investigación Masira, Bucaramanga, Colombia.
  • Visser L; Universidad de Santander, Facultad de Ciencias Médicas y de la Salud, Instituto de Investigación Masira, Bucaramanga, Colombia.
  • Rueda-Forero NJ; NBC Núcleo de Biotecnología Curauma, Pontificia Universidad Católica de Valparaíso, Campus Curauma, Av. Universidad 330, Valparaíso, Chile.
Biosci Rep ; 41(12)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1526113
ABSTRACT
Parasporin-2Aa1 (PS2Aa1) is a toxic protein of 37 KDa (30 kDa, activated form produced by proteolysis) that was shown to be cytotoxic against specific human cancer cells, although its mechanism of action has not been elucidated yet. In order to study the role of some native peptide fragments of proteins on anticancer activity, here we investigated the cytotoxic effect of peptide fragments from domain-1 of PS2Aa1 and one of the loops present in the binding region of the virus spike protein from Alphacoronavirus (HCoV-229E), the latter according to scientific reports, who showed interaction with the human APN (h-APN) receptor, evidence corroborated through computational simulations, and thus being possible active against colon cancer cells. Peptides namely P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa were synthesized using the Fmoc solid-phase synthesis and characterized by mass spectrometry (MS). Additionally, one region from loop 1 of HCoV-229E, Loop1-HCoV-229E, was also synthesized and characterized. The A4W-GGN5 anticancer peptide and 5-fluorouracil (5-FU) were taken as a control in all experiments. Circular dichroism revealed an α-helix structure for the peptides derived from PS2Aa1 (P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa) and ß-laminar structure for the peptide derived from Alphacoronavirus spike protein Loop1-HCoV-229E. Peptides showed a hemolysis percentage of less than 20% at 100 µM concentration. Besides, peptides exhibited stronger anticancer activity against SW480 and SW620 cells after exposure for 48 h. Likewise, these compounds showed significantly lower toxicity against normal cells CHO-K1. The results suggest that native peptide fragments from Ps2Aa1 may be optimized as a novel potential cancer-therapeutic agents.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptide Fragments / Colorectal Neoplasms / Endotoxins / Spike Glycoprotein, Coronavirus / Antineoplastic Agents Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: BSR20211964

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptide Fragments / Colorectal Neoplasms / Endotoxins / Spike Glycoprotein, Coronavirus / Antineoplastic Agents Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: BSR20211964