Helical motifs are key structural elements in many biological functions involving protein-protein interactions. Helixes are characterizaed by a central polypeptide backbone which serve to project, along individual faces, the hot residues involved in the selective and specific recognition. a,a disubstsituted amino acids are typpically used in the preparation of beckbone peptidomimetics reproducing helical topography, being Aib the most rapresentative element of this class. Despite the large number of cycloalkane derivatis used in the preparation of conformationally constrained helis mimics, few examples are reported on azacyclic amino acids. Here we present a very efficient synthesis of orthogonally protected 1H-azepine-4- amino-4-carboxylic acid (Azn), a conformationally restricted ornithine analogue. azn was used to prepare two pentapeptides containing Ala and Aib. Both computational and spectrosscopic data (CD/NMR) showed that the stereochemistry at Ca plays an important role in determining the conformational preferences of Azn peptides. In particular, (R).Azn revelead the capability to drive the folding toward a well defined 310 helix secondary structure.
Ahead of the curve : helical behaviour of 1H-azepine-4-amino-4-carboxylic acid, a new a, a-disubstituted ornithine analogue / S. Pellegrino, A. Contini, M.L. Gelmi. ((Intervento presentato al convegno COST action on Foldamers tenutosi a Regensburg nel 2012.
Ahead of the curve : helical behaviour of 1H-azepine-4-amino-4-carboxylic acid, a new a, a-disubstituted ornithine analogue
S. PellegrinoPrimo
;A. ContiniSecondo
;M.L. GelmiUltimo
2012
Abstract
Helical motifs are key structural elements in many biological functions involving protein-protein interactions. Helixes are characterizaed by a central polypeptide backbone which serve to project, along individual faces, the hot residues involved in the selective and specific recognition. a,a disubstsituted amino acids are typpically used in the preparation of beckbone peptidomimetics reproducing helical topography, being Aib the most rapresentative element of this class. Despite the large number of cycloalkane derivatis used in the preparation of conformationally constrained helis mimics, few examples are reported on azacyclic amino acids. Here we present a very efficient synthesis of orthogonally protected 1H-azepine-4- amino-4-carboxylic acid (Azn), a conformationally restricted ornithine analogue. azn was used to prepare two pentapeptides containing Ala and Aib. Both computational and spectrosscopic data (CD/NMR) showed that the stereochemistry at Ca plays an important role in determining the conformational preferences of Azn peptides. In particular, (R).Azn revelead the capability to drive the folding toward a well defined 310 helix secondary structure.Pubblicazioni consigliate
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