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 binding with 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 / Sernissi, Lorenzo; Ricci, Luciano; Scarpi, Dina; Bianchini, Francesca; Arosio, Daniela; Contini, Alessandro*; Occhiato, Ernesto G.. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - STAMPA. - 16:(2018), 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
Sernissi, Lorenzo;Scarpi, Dina;Bianchini, Francesca;Occhiato, Ernesto G.
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 binding with 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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