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

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)995-1004
Number of pages10
JournalJournal of Chemical Information and Modeling
Issue number2
Publication statusPublished - 24 Feb 2020

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering
  • Computer Science Applications
  • Library and Information Sciences


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