Insight to the binding mode of triazole RGD-peptidomimetics to integrin-rich cancer cells by NMR and molecular modeling. Issue 5 (1st March 2016)

• Record Type: Journal Article
• Authors: Vasile, Francesca; Menchi, Gloria; Lenci, Elena; Guarna, Antonio; Potenza, Donatella; Trabocchi, Andrea
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 5(2016)
• Page Start: 989
• Page End: 994
• Publication Date: 2016-03-01
• Subjects: Small molecule -- STD-NMR -- Molecular docking -- Ligand–protein interaction -- Angiogenesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.01.023
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: The binding features of a novel class of 'click chemistry'-derived RGD mimics with integrin ligand capability were studied toward αv β3 integrin using STD-NMR techniques on intact integrin-rich ECV340 bladder cancer cell line. STD is useful to identify which moieties of the ligand are closest to the receptor in the bound state. The NMR data were integrated with competitive binding assays to the purified αv β3 receptor and were interpreted with the aid of docking calculations. The involvement of the triazole hydrogen atom in the interaction with the receptor was evinced for all compounds but2, in agreement with docking studies showing a certain proximity between triazole and Tyr178. Moreover, the interaction of the hydroxylated ligands with the receptor was not as extended as in the compounds belonging to the corresponding series, with the exception of compound4 having 2-aminobenzimidazole as the arginine bioisostere, in agreement with biological assay results showing reduced binding capability for the hydroxylated peptidomimetics.