Fluorescence study for selecting specific ligands toward HER2 receptor: An example of receptor fragment approach

• Published in: European journal of medicinal chemistry Vol. 61; pp. 116 - 121
• Main Authors: Calce, Enrica, Monfregola, Luca, Sandomenico, Annamaria, Saviano, Michele, De Luca, Stefania
• Format: Journal Article
• Language: English
• Published: PARIS Elsevier Masson SAS 01.03.2013; Elsevier
• Subjects: Antibodies, Monoclonal, Humanized - chemistry; Antibodies, Monoclonal, Humanized - pharmacology; Chemistry, Medicinal; Crystallography, X-Ray; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Fluorescence; Fluorescence study; Her2 receptor; Humans; Life Sciences & Biomedicine; Ligands; Models, Molecular; Molecular Structure; Peptides - chemical synthesis; Peptides - chemistry; Peptides - isolation & purification; Peptides - pharmacology; Pharmacology & Pharmacy; Receptor fragment model; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - chemistry; Receptor, ErbB-2 - metabolism; Science & Technology; Selective ligands; Spectrometry, Fluorescence; Structure-Activity Relationship; Trastuzumab; Fluorescence study; Receptor fragment model; Her2 receptor; Selective ligands; PROTEIN; TRASTUZUMAB; PHAGE DISPLAY; OVARIAN-CANCER; BREAST-CANCER CELLS; COMBINED BIOLOGICAL THERAPY; CARCINOMAS; EXPRESSION; BINDING; ENDOTHELIAL GROWTH-FACTOR
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2012.09.024

Fluorescence titrations allowed us to study the interaction process between Herceptin (Fab)-derived peptides and a synthetic peptide mimicking a subdomain IV of the receptor HER2 (HER2-DIVMP). For some of the investigated peptide/HER2-DIVMP complexes a nanomolar dissociation constant was found. The performed interaction studies were completely immune from interferences of other receptor domains not covered by the design, thus decreasing the possibilities of selecting potential ligands able to bind other subtypes of HER2 receptor family. Our results demonstrate that the adopted receptor fragment approach represents an efficient methodology for selecting new molecules as lead structures specific for the receptor target. For these reasons the optimized compounds could be employed as delivery agents for the receptor-mediated anticancer therapy. [Display omitted] Fluorescence studies allowed the selection of ligands highly specific for domain IV of HER2 receptor. This methodology, which used the receptor fragment approach, proved to be a reliable screening technique. ► Receptor fragment approach was adopted. ► Peptide ligands selected for HER2 domain IV were developed. ► Fluorescence spectroscopy revealed to be fast and sensitive technique.