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Design and validation of neuronal exocytosis blocking peptides as potential novel antiperspirants.
Butron, Laura; Nikolaeva-Koleva, Magdalena; Sempere, Ana; Rivero, Verónica; Fernandez-Ballester, Gregorio; Espinosa, Ana; Vergassola, Matteo; Mastrocola, Elena; Zucchi, Sara; Ragni, Lorella; Fernández-Carvajal, Asia; Mangano, Giorgina; Ferrer-Montiel, Antonio; Devesa, Isabel.
Afiliación
  • Butron L; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, 03202 Elche, Alicante, Spain.
  • Nikolaeva-Koleva M; AntalGenics SL, Ed. Quorum III, UMH Scientific Park, 03202 Elche, Alicante, Spain.
  • Sempere A; AntalGenics SL, Ed. Quorum III, UMH Scientific Park, 03202 Elche, Alicante, Spain.
  • Rivero V; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, 03202 Elche, Alicante, Spain.
  • Fernandez-Ballester G; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, 03202 Elche, Alicante, Spain.
  • Espinosa A; AntalGenics SL, Ed. Quorum III, UMH Scientific Park, 03202 Elche, Alicante, Spain.
  • Vergassola M; Angelini Pharma S.p.A. Global R&D PLCM Preclinical Development, Ancona, Italy.
  • Mastrocola E; Angelini Pharma S.p.A. Global R&D PLCM Preclinical Development, Ancona, Italy.
  • Zucchi S; Angelini Pharma S.p.A. Global R&D PLCM Preclinical Development, Ancona, Italy.
  • Ragni L; Angelini Pharma S.p.A. Global R&D PLCM Preclinical Development, Ancona, Italy.
  • Fernández-Carvajal A; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, 03202 Elche, Alicante, Spain.
  • Mangano G; Senior Scientific Consultant, Rome, Italy.
  • Ferrer-Montiel A; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, 03202 Elche, Alicante, Spain.
  • Devesa I; AntalGenics SL, Ed. Quorum III, UMH Scientific Park, 03202 Elche, Alicante, Spain.
Exp Dermatol ; 32(7): 999-1006, 2023 07.
Article en En | MEDLINE | ID: mdl-37009806
Thermoregulation and heat dissipation by sweat production and evaporation are vital for human survival. However, hyperhidrosis or excessive perspiration might affect people's quality of life by causing discomfort and stress. The prolonged use of classical antiperspirants, anticholinergic medications or botulinum toxin injections for persistent hyperhidrosis might produce diverse side effects that limit their clinical use. Inspired by botox molecular mode of action, we used an in silico molecular modelling approach to design novel peptides to target neuronal acetylcholine exocytosis by interfering with the Snapin-SNARE complex formation. Our exhaustive design rendered the selection of 11 peptides that decreased calcium-dependent vesicle exocytosis in rat DRG neurons, reducing αCGRP release and TRPV1 inflammatory sensitization. The most potent peptides were palmitoylated peptides SPSR38-4.1 and SPSR98-9.1 that significantly suppressed acetylcholine release in vitro in human LAN-2 neuroblastoma cells. Noteworthy, local acute and chronic administration of SPSR38-4.1 peptide significantly decreased, in a dose-dependent manner, pilocarpine-induced sweating in an in vivo mouse model. Taken together, our in silico approach lead to the identification of active peptides able to attenuate excessive sweating by modulating neuronal acetylcholine exocytosis, and identified peptide SPSR38-4.1 as a promising new antihyperhidrosis candidate for clinical development.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Antitranspirantes / Hiperhidrosis Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Exp Dermatol Asunto de la revista: DERMATOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: España

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Antitranspirantes / Hiperhidrosis Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Exp Dermatol Asunto de la revista: DERMATOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: España