Preferred 3D-structure of peptides rich in a severely conformationally restricted cyclopropane analogue of phenylalanine.
Terminally blocked, homo-peptide amides of (R,R)-1-amino-2,3-diphenylcyclopropane-1-carboxylic acid (c3diPhe), a chiral member of the family of Calpha-tetrasubstituted alpha-amino acids, from the dimer to the tetramer, and diastereomeric co-oligopeptides of (R,R)- or (S,S)-c3diPhe with (S)-alanine residues to the trimer level were prepared in solution and fully characterized. The synthetic effort was extended to terminally protected co-oligopeptide esters to the hexamer, where c3diPhe residues are combined with achiral alpha-aminoisobutyric acid residues. The preferred conformations of the peptides were assessed in solution by FT-IR absorption, NMR, and CD techniques, and for seven oligomers in the crystal state (by X-ray diffraction) as well. This study clearly indicates that c3diPhe, a sterically demanding cyclopropane analogue of phenylalanine, tends to fold peptides into beta-turn and 3(10)-helix conformations. However, when c3diPhe is in combination with other chiral residues, the conformation preferred by the resulting peptides is also dictated by the chiral sequence of the amino acid building blocks. The (S,S)-enantiomer of this alpha-amino acid, unusually lacking asymmetry in the main chain, strongly favors the left-handedness of the turn/helical peptides formed.
Crisma
Marco
M
Institute of Biomolecular Chemistry, CNR, Department of Chemistry, University of Padova via Marzolo 1, 35131 Padova, Italy.
De Borggraeve
Wim M
WM
Peggion
Cristina
C
Formaggio
Fernando
F
Royo
Soledad
S
Jiménez
Ana I
AI
Cativiela
Carlos
C
Toniolo
Claudio
C
D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D003521:Cyclopropanes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry*; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared
D003521:Cyclopropanes; D010446:Peptide Fragments; D010649:Phenylalanine; C030797:cyclopropane