Structural versatility of peptides from C alpha, alpha-disubstituted glycines: crystal-state conformational analysis of peptides from C alpha-methylhomophenylalanine, (alpha Me) Hph.
The molecular and crystal structures of the C alpha-tetrasubstituted, delta-branched alpha-amino acid C alpha-methylhomophenylalanine, H-D-(alpha Me)Hph-OH, and three peptides (to the pentamer level), including the homotripeptide, have been determined by X-ray diffraction. The peptides are Z-L-(alpha Me)Hph-(L-Ala)2-OMe pBrBz-[D-(alpha Me)Hph]3-OtBu and Ac-(Aib)2-L-(alpha Me)Hph-(Aib)2-OtBu. All the (alpha Me)Hph residues prefer phi, psi torsion angles in the helical region of the conformational map. The two terminally blocked tripeptides adopt a beta-bend conformation stabilized by a 1<--4 C = O... H-N intramolecular H-bond. The terminally blocked pentapeptide is folded in a regular 3(10)-helix. In general, the relationship between (alpha Me)Hph alpha-carbon chirality and helix handedness is the same as that exhibited by protein amino acids. A comparison is also made with the conclusions extracted from published work on peptides from other types of C alpha-alkylated aromatic alpha-amino acids.
Doi
M
M
Osaka University of Pharmaceutical Sciences, Japan.
Ishida
T
T
Polese
A
A
Formaggio
F
F
Crisma
M
M
Toniolo
C
C
Broxterman
Q B
QB
Kamphuis
J
J
D000613:Aminobutyrates; D018360:Crystallography, X-Ray; D005998:Glycine / Q000031:analogs & derivatives*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010649:Phenylalanine / Q000031:analogs & derivatives*; D017433:Protein Structure, Secondary
D000613:Aminobutyrates; D010455:Peptides; D010649:Phenylalanine; C014328:2-amino-4-phenylbutyric acid; D005998:Glycine