Configurationally driven folding of model tetrapeptides containing L- or D-morpholine-3-carboxylic acids as beta-turn nucleators.
The conformational analysis by NMR, IR, and molecular modeling of tetrapeptides containing morpholine-3-carboxylic acid (Mor) as a proline surrogate is presented. The relationship between the chirality of the cyclic amino acid at position i+1 and the turn propensity is maintained with respect to the reference proline-containing peptides, although marked differences in the type of folded structures were observed. The conformational profile of morpholine-containing turn peptides as a function of the chirality of the cyclic amino acid indicated that the heterochiral tetrapeptide containing the D-isomer of the cyclic amino acid is more prone to nucleate compact folded structures, although with no resemblance to the beta-turn structures of D-proline-containing peptides. Also, the solvation system proved to influence the organization of folded structures, as in the more interactive CD(3)CN the model peptides showed more compact conformations. The L-Mor-containing peptide displayed two rotamers at the Val-Mor amide bond. The trans isomer did not experience any turn structures, nor any intramolecular hydrogen-bonds, whereas the cis isomer showed a strong preference for a type VI beta-turn structure, thus providing a different conformational asset with respect to the beta-turn structure as reported for the reference L-proline model peptide.
Trabocchi
Andrea
A
Department of Organic Chemistry Ugo Schiff, University of Florence, Polo Scientifico e Tecnologico, I-50019 Sesto Fiorentino, Florence, Italy. andrea.trabocchi@unifi.it
Sladojevich
Filippo
F
Guarna
Antonio
A
D000596:Amino Acids / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D000596:Amino Acids; D002264:Carboxylic Acids; D010455:Peptides