Tetrahydroisoquinoline-4-carboxylic acid, a constrained β2-amino acid named β-TIC, was for the first time synthesized in enantiopure form. The biocatalytic route here applied represents one of the few successful examples of enzymatic resolution of β2-amino acids. Model tetrapeptides, i.e. Fmoc-L-Ala-β-TIC-β-Ala-L-Val-OBn, containing both isomers of β-TIC, were prepared. Both computational and NMR studies were performed. A reverse-turn conformation was observed in the case of R-β-TIC enantiomer, the enantiomer obtained in 99% e.e. by enzymatic resolution. β-TIC/β-Ala construct represents the first example of a flexible turn mimetic containing a cyclic and an acyclic β-amino acid. Furthermore, the presence of an aromatic ring of β-TIC could facilitate non-covalent interactions increasing the potential of this scaffold for the preparation of protein-protein interaction modulators.
Tandem tetrahydroisoquinoline-4-carboxylic acid/β-alanine as a new construct able to induce a flexible turn / M.L. Gelmi, A. Contini, A. Bonetti, R. Bucci, D. Tessaro, F. Clerici, S. Pellegrino, D. Nava. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 23:45(2017 Aug), pp. 10822-10831.
Tandem tetrahydroisoquinoline-4-carboxylic acid/β-alanine as a new construct able to induce a flexible turn
M.L. GelmiUltimo
;A. Contini;A. BonettiSecondo
;R. BucciPrimo
;F. Clerici;S. Pellegrino;D. Nava
2017
Abstract
Tetrahydroisoquinoline-4-carboxylic acid, a constrained β2-amino acid named β-TIC, was for the first time synthesized in enantiopure form. The biocatalytic route here applied represents one of the few successful examples of enzymatic resolution of β2-amino acids. Model tetrapeptides, i.e. Fmoc-L-Ala-β-TIC-β-Ala-L-Val-OBn, containing both isomers of β-TIC, were prepared. Both computational and NMR studies were performed. A reverse-turn conformation was observed in the case of R-β-TIC enantiomer, the enantiomer obtained in 99% e.e. by enzymatic resolution. β-TIC/β-Ala construct represents the first example of a flexible turn mimetic containing a cyclic and an acyclic β-amino acid. Furthermore, the presence of an aromatic ring of β-TIC could facilitate non-covalent interactions increasing the potential of this scaffold for the preparation of protein-protein interaction modulators.File | Dimensione | Formato | |
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