Tandem Tetrahydroisoquinoline-4-carboxylic Acid/ß-Alanine as a New Construct Able To Induce a Flexible Turn.
Chemistry
; 23(45): 10822-10831, 2017 Aug 10.
Article
em En
| MEDLINE
| ID: mdl-28467649
ABSTRACT
Tetrahydroisoquinoline-4-carboxylic acid, a constrained ß2 -amino acid named ß-TIC, was synthesised for the first time in enantiopure form. The biocatalytic route applied herein represents one of the few successful examples of enzymatic resolution of ß2 -amino acids. Model tetrapeptides, namely, Fmoc-l-Ala-ß-TIC-ß-Ala-l-Val-OBn (Fmoc=fluorenylmethyloxycarbonyl, Bn=benzyl), containing both isomers of ß-TIC, were prepared. Both computational and NMR spectroscopy studies were performed. A reverse-turn conformation was observed in the case of (R)-ß-TIC enantiomer that was obtained in 99 % enantiomeric excess by enzymatic resolution. The ß-TIC/ß-Ala construct represents the first example of a flexible turn mimetic containing a cyclic and an acyclic ß-amino acid. Furthermore, the presence of an aromatic ring of ß-TIC could facilitate non-covalent interactions to increase the potential of this scaffold for the preparation of protein-protein interaction modulators.
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01-internacional
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MEDLINE
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article