SPR and NMR characterization of the molecular interaction between A9 peptide and a model system of HER2 receptor: A fragment approach for selecting peptide structures specific for their target. (20th November 2019)

• Record Type: Journal Article
• Authors: De Luca, Stefania; Verdoliva, Valentina; Saviano, Michele; Fattorusso, Roberto; Diana, Donatella
• Is Part Of: Journal of peptide science. Volume 26:Number 2(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-11-20
• Subjects: : HER2 receptor -- saturation transfer difference -- surface plasmon resonance -- synthetic receptor model -- trNOESY; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.3231
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : The binding process of A9 peptide toward HER2‐DIVMP, a synthetic model of the receptor domain IV, was studied by using the surface plasmon resonance (SPR) technique, with the aim of validating it as a fast and reliable screening method for selecting peptide ligands specifically targeting a domain of their target. To investigate the structural basis of A9 binding to the model of HER2‐DIVMP, multiple ligand‐based nuclear magnetic resonance (NMR) methods were applied. The use of saturation transfer difference (STD) and WaterLOGSY NMR experiments identified key residues in the peptide for the receptor binding. Moreover, the bound conformation of the A9 peptide was obtained using transferred nuclear Overhauser effect spectroscopy (trNOESY) experiments. The NMR data revealed an extended binding surface that confirms an in silico model previously reported. These structural findings could provide good starting points for future lead structures optimization specific for the receptor target. Abstract : The SPR technique as a fast and reliable method for characterizing the binding process for the complex A9/HER2‐DIVMP was assessed. The NMR ligand‐based techniques allowed the identification of the portions of A9 in closest contact with the receptor model HER2‐DIVMP and of the bound peptide preferred conformations. These results demonstrated that a site‐tailored screening method of potential peptide ligands was successfully tuned