Rational Design and in Vitro Evaluation of Novel Peptides Binding to Neuroligin-1 for Synaptic Targeting

Pilar Vásquez, Felipe Vidal, Josefa Torres, Verónica A. Jiménez, Leonardo Guzmán

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

1 Cita (Scopus)

Resumen

Neuroligin-1 (NL1) is a postsynaptic cell adhesion protein that plays a crucial role in synapsis and signaling between neurons. Due to its clustered distribution in synaptic clefts, NL1 appears as a novel potential site for synaptic targeting purposes. In this work, in silico protein topography analysis was employed to identify two prospective binding sites on the NL1 dimer surface in the 2:2 synaptic adhesion complex with β-neurexin (PDB code 3B3Q). Receptor-based rational design, cell-penetrating capability prediction, molecular docking, molecular dynamics simulations, and binding free energy calculations were used to identify five heptapeptides candidates with favorable predicted profiles as non cell-penetrating NL1-binding agents. Preliminary in vitro colocalization assays with NL1-transfected HEK 293 cells confirmed that peptides remain in the extracellular space without inducing detectable changes in cell morphology. The highest NL1-colocatization capability was attained by the peptide ADEAIVA, which appears as a promising candidate for the future development of specific NL1-targeting systems as part of synapse-directed therapies against central nervous system diseases.

Idioma originalInglés
Páginas (desde-hasta)995-1004
Número de páginas10
PublicaciónJournal of Chemical Information and Modeling
Volumen60
N.º2
DOI
EstadoPublicada - 24 feb 2020

Áreas temáticas de ASJC Scopus

  • Química (todo)
  • Ingeniería química (todo)
  • Informática aplicada
  • Biblioteconomía y ciencias de la información

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