Synthesis of U-theraphotoxin-Pv1a_1, an Aedes aegypti larvicidal disulfide bridged peptide from the Colombian tarantula Pamphobeteus verdolaga (Araneae: Theraphosidae)

The attention to the increased resistance of Aedes aegipty to traditional insecticides has been directed to the development of bioinsecticides, such as those produced by insect predators, e.g. spiders. Here we present the solid-phase synthesis of native U-theraphotoxin-Pv1a_1 (n-Pv1a_1) from Pamphob...

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Main Authors: Sebastián Estrada-Gómez, Cristian Salinas-Restrepo, Leidy Johana Vargas-Muñoz, Fanny Guzmán, Cesar Segura, Davinia Pla, Libia Sanz, Juan J Calvete
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Toxicon: X
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590171025000116
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author Sebastián Estrada-Gómez
Cristian Salinas-Restrepo
Leidy Johana Vargas-Muñoz
Fanny Guzmán
Cesar Segura
Davinia Pla
Libia Sanz
Juan J Calvete
author_facet Sebastián Estrada-Gómez
Cristian Salinas-Restrepo
Leidy Johana Vargas-Muñoz
Fanny Guzmán
Cesar Segura
Davinia Pla
Libia Sanz
Juan J Calvete
author_sort Sebastián Estrada-Gómez
collection DOAJ
description The attention to the increased resistance of Aedes aegipty to traditional insecticides has been directed to the development of bioinsecticides, such as those produced by insect predators, e.g. spiders. Here we present the solid-phase synthesis of native U-theraphotoxin-Pv1a_1 (n-Pv1a_1) from Pamphobeteus verdolaga, an active (by contact) insecticidal peptide against A. aegipty. U-theraphotoxin-Pv1a_1 sequence was gathered from venom proteomics and venom gland transcriptomics of Pamphobeteus verdolaga, and synthesized by solid phase using the Fmoc strategy followed by dimethyl sulfoxide promoted native disulfide bond formation. The synthetic peptide (s-Pv1a_1) was assayed for larvicidal activity in II and III instar A. aegypti larvae, as well as for cytotoxicity in human red blood and HaCat cells. s-Pv1a_1 showed potent activity towards A. aegypti larvae in the micro molar range, while showing no hemolytic activity and mild cytotoxicity to HaCat cells. Its potent contact activity makes n-Pv1a_1 and its synthetic version, s-Pv1a, promising biopesticides for the control of mosquito populations.
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spelling doaj-art-5e5211472e734aee9ebc0a4f1e99cc5d2025-08-20T03:09:42ZengElsevierToxicon: X2590-17102025-06-012610022410.1016/j.toxcx.2025.100224Synthesis of U-theraphotoxin-Pv1a_1, an Aedes aegypti larvicidal disulfide bridged peptide from the Colombian tarantula Pamphobeteus verdolaga (Araneae: Theraphosidae)Sebastián Estrada-Gómez0Cristian Salinas-Restrepo1Leidy Johana Vargas-Muñoz2Fanny Guzmán3Cesar Segura4Davinia Pla5Libia Sanz6Juan J Calvete7Grupo de Toxinología y Alternativas Terapeuticas y Alimentarias - Serpentario, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Colombia, Medellin, 050010, Antioquia, Colombia; Centro de Investigación en Recursos Naturales y Sustentabilidad, Universidad Bernardo O'Higgins, Avenida Viel 1497, Santiago, Chile; Corresponding author. Grupo de Toxinología y Alternativas Terapeuticas - Serpentario, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Colombia, Medellin, 050010, Antioquia, Colombia.Grupo de Toxinología y Alternativas Terapeuticas y Alimentarias - Serpentario, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Colombia, Medellin, 050010, Antioquia, ColombiaFacultad de Medicina, Universidad Cooperativa de Colombia, Medellin, Antioquia, ColombiaNúcleo Biotecnología Curauma, Pontificia Universidad Católica de Valparaíso, Valparaíso, 2373223, ChileUnidad de Espectrometría de Masas, Sede de Investigación Universitaria, Universidad de Antioquia UdeA, Medellín, 050010, ColombiaEvolutionary and Translational Venomics Laboratory, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Valencia, SpainEvolutionary and Translational Venomics Laboratory, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Valencia, SpainEvolutionary and Translational Venomics Laboratory, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Valencia, SpainThe attention to the increased resistance of Aedes aegipty to traditional insecticides has been directed to the development of bioinsecticides, such as those produced by insect predators, e.g. spiders. Here we present the solid-phase synthesis of native U-theraphotoxin-Pv1a_1 (n-Pv1a_1) from Pamphobeteus verdolaga, an active (by contact) insecticidal peptide against A. aegipty. U-theraphotoxin-Pv1a_1 sequence was gathered from venom proteomics and venom gland transcriptomics of Pamphobeteus verdolaga, and synthesized by solid phase using the Fmoc strategy followed by dimethyl sulfoxide promoted native disulfide bond formation. The synthetic peptide (s-Pv1a_1) was assayed for larvicidal activity in II and III instar A. aegypti larvae, as well as for cytotoxicity in human red blood and HaCat cells. s-Pv1a_1 showed potent activity towards A. aegypti larvae in the micro molar range, while showing no hemolytic activity and mild cytotoxicity to HaCat cells. Its potent contact activity makes n-Pv1a_1 and its synthetic version, s-Pv1a, promising biopesticides for the control of mosquito populations.http://www.sciencedirect.com/science/article/pii/S2590171025000116ProteomicSynthetic peptideInhibitory cysteine knotLarvicidalPamphobeteus
spellingShingle Sebastián Estrada-Gómez
Cristian Salinas-Restrepo
Leidy Johana Vargas-Muñoz
Fanny Guzmán
Cesar Segura
Davinia Pla
Libia Sanz
Juan J Calvete
Synthesis of U-theraphotoxin-Pv1a_1, an Aedes aegypti larvicidal disulfide bridged peptide from the Colombian tarantula Pamphobeteus verdolaga (Araneae: Theraphosidae)
Toxicon: X
Proteomic
Synthetic peptide
Inhibitory cysteine knot
Larvicidal
Pamphobeteus
title Synthesis of U-theraphotoxin-Pv1a_1, an Aedes aegypti larvicidal disulfide bridged peptide from the Colombian tarantula Pamphobeteus verdolaga (Araneae: Theraphosidae)
title_full Synthesis of U-theraphotoxin-Pv1a_1, an Aedes aegypti larvicidal disulfide bridged peptide from the Colombian tarantula Pamphobeteus verdolaga (Araneae: Theraphosidae)
title_fullStr Synthesis of U-theraphotoxin-Pv1a_1, an Aedes aegypti larvicidal disulfide bridged peptide from the Colombian tarantula Pamphobeteus verdolaga (Araneae: Theraphosidae)
title_full_unstemmed Synthesis of U-theraphotoxin-Pv1a_1, an Aedes aegypti larvicidal disulfide bridged peptide from the Colombian tarantula Pamphobeteus verdolaga (Araneae: Theraphosidae)
title_short Synthesis of U-theraphotoxin-Pv1a_1, an Aedes aegypti larvicidal disulfide bridged peptide from the Colombian tarantula Pamphobeteus verdolaga (Araneae: Theraphosidae)
title_sort synthesis of u theraphotoxin pv1a 1 an aedes aegypti larvicidal disulfide bridged peptide from the colombian tarantula pamphobeteus verdolaga araneae theraphosidae
topic Proteomic
Synthetic peptide
Inhibitory cysteine knot
Larvicidal
Pamphobeteus
url http://www.sciencedirect.com/science/article/pii/S2590171025000116
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