Turn stabilization in short peptides by C(alpha)-methylated alpha-amino acids.
The crystal-state conformations of three protected tripeptides, four tetrapeptides, and one pentapeptide, heavily based on the chiral C(alpha)-methylated alpha-amino acids Iva, (alpha Me)Nva, and (Me)Val, were assessed by X-ray diffraction analyses. The eight peptide sequences are as follows: Z-(D-Iva)2-D-Val-OMe, Z-D-Iva-L-Iva-Gly-OtBu, Z-L-Pro-D-Iva-L-Iva-Gly-OtBu, Z-L-Pro-L-Iva-D-Iva-Gly-OtBu, Z-Aib-[L-(alpha Me)Nva]2-OtBu, Ac-[L-(alpha Me)Val]3-D-(alpha Me)Val-OtBu, Z-[L-(alpha Me)Val]4-OH, and Z-L-Ala-[L-(alpha Me)Nva]4-OtBu. Two independent molecules were observed in the asymmetric units of Z-D-Iva-L-Iva-Gly-OtBu and Z-Aib-[L-(alpha Me)Nva]2-OtBu, while three independent molecules were seen in Z-L-Ala-[L-(alpha Me)Nva]4-OtBu. All peptides are folded in a single or multiple beta-turn conformations. Interestingly: (i) a water bridge within the N-terminal beta-turn is seen in Z-L-Pro-L-Iva-D-Iva-Gly-OtBu (dihydrate), and (ii) the hydroxyl group of the C-terminal carboxyl functionality of Z-[L-(alpha Me)Val]4-OH generates an oxy-analogue of a beta-turn. The N-terminal beta-turn is missing in molecules A and B, but it does occur, although poorly stabilized, in molecule C, of Z-L-Ala-[L-(alpha Me)Nva]4-OtBu.
Crisma
Marco
M
Institute of Biomolecular Chemistry, CNR, Department of Chemistry, University of Padova, 35131 Padova, Italy. marco.crisma@unipd.it
Moretto
Alessandro
A
De Zotti
Marta
M
Formaggio
Fernando
F
Kaptein
Bernard
B
Broxterman
Quirinus B
QB
Toniolo
Claudio
C
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D018360:Crystallography, X-Ray; D008745:Methylation; D008958:Models, Molecular; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000596:Amino Acids; D009842:Oligopeptides