Por favor, use este identificador para citar o enlazar este documento: https://hdl.handle.net/2445/121314
Título: Toward a novel drug to target the EGF-EGFR interaction: design of metabolically stable bicyclic peptides
Autor: Guardiola Bagán, Salvador
Seco Moral, Jesús
Varese, Monica
Díaz Lobo, Mireia
García Arroyo, Jesús
Teixidó Turà, Meritxell
Nevola, Laura
Giralt Lledó, Ernest
Materia: Càncer
Pèptids
Proteïnes
Cancer
Peptides
Proteins
Fecha de publicación: 6-nov-2017
Publicado por: Wiley-VCH
Resumen: In cancer, proliferation of malignant cells is driven by overactivation of growth-signalling mechanisms, such as the epidermal growth factor receptor (EGFR) pathway. Despite its therapeutic relevance, the EGF-EGFR interaction has remained elusive to inhibition by synthetic molecules, mostly as a result of its large size and lack of binding pockets and cavities. Designed peptides, featuring cyclic motifs and other structural constraints, have the potential to modulate such challenging protein-protein interactions (PPIs). Herein, we present the structure-based design of a series of bicyclic constrained peptides that mimic an interface domain of EGFR and inhibit the EGF-EGFR interaction by targeting the smaller partner (i.e., EGF). This design process was guided by the integrated use of in silico methods and biophysical techniques, such as NMR spectroscopy and surface acoustic wave. The best analogues were able to reduce selectively the viability of EGFR+ human cancer cells. In addition to their efficacy, these bicyclic peptides are endowed with exceptional stability and metabolic resistance-two features that make them suitable candidates for in vivo applications.
Nota: Versió postprint del document publicat a: https://doi.org/10.1002/cbic.201700519
Es parte de: ChemBioChem, 2018, vol. 4, num. 19, p. 76-84
URI: https://hdl.handle.net/2445/121314
Recurso relacionado: https://doi.org/10.1002/cbic.201700519
ISSN: 1439-4227
Aparece en las colecciones:Articles publicats en revistes (Química Inorgànica i Orgànica)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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