A stereodivergent strategy was devised to obtain enantiopure cis and trans 5-aminopipecolic acids (5-APAs) in suitably protected forms to be employed in peptide synthesis as conformationally constrained α- and δ-amino acids. The cis isomer was used as a δ-amino acid to construct a cyclic RGD-containing peptidomimetic, the ability of which to compete with biotinylated vitronectin for the binding to the isolated αVβ3 integrin was measured (IC50 = 4.2 ± 0.9 nM). A complete 1H NMR and computational conformational analysis was performed to elucidate the reasons for the high affinity of this cyclic peptidomimetic in comparison with Cilengitide.
Stereodivergent Synthesis of 5-Aminopipecolic Acids and Application in the Preparation of a Cyclic RGD Peptidomimetic as a nanomolar αVβ3 Integrin Ligand / L. Sernissi, L. Ricci, D. Scarpi, F. Bianchini, D. Arosio, A. Contini, E.G. Occhiato. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0539. - 16:18(2018 May 09), pp. 3402-3414. [10.1039/C8OB00534F]
Stereodivergent Synthesis of 5-Aminopipecolic Acids and Application in the Preparation of a Cyclic RGD Peptidomimetic as a nanomolar αVβ3 Integrin Ligand
A. Contini
Penultimo
;
2018
Abstract
A stereodivergent strategy was devised to obtain enantiopure cis and trans 5-aminopipecolic acids (5-APAs) in suitably protected forms to be employed in peptide synthesis as conformationally constrained α- and δ-amino acids. The cis isomer was used as a δ-amino acid to construct a cyclic RGD-containing peptidomimetic, the ability of which to compete with biotinylated vitronectin for the binding to the isolated αVβ3 integrin was measured (IC50 = 4.2 ± 0.9 nM). A complete 1H NMR and computational conformational analysis was performed to elucidate the reasons for the high affinity of this cyclic peptidomimetic in comparison with Cilengitide.File | Dimensione | Formato | |
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