Peptides from chiral C alpha,alpha-disubstituted glycines. Crystallographic characterization of conformation of C alpha-methyl, C alpha-isopropylglycine [(alpha Me)Val] in simple derivatives and model peptides.
The molecular and crystal structures of one derivative and three model peptides (to the pentapeptide level) of the chiral C alpha,alpha-disubstituted glycine C alpha-methyl, C alpha-isopropylglycine [(alpha Me)Val] have been determined by X-ray diffraction. The derivative is mClAc-L-(alpha Me)Val-OH, and the peptides are Z-L-(alpha Me)Val-(L-Ala)2-OMe monohydrate, Z-Aib-L-(alpha Me)Val-(Aib)2-OtBu, and Ac-(Aib)2-L-(alpha Me)Val-(Aib)2OtBu acetonitrile solvate. The tripeptide adopts a type-I beta-turn conformation stabilized by a 1----4N--H...O = C intramolecular H-bond. The tetra- and pentapeptides are folded in regular right-handed 3(10)-helices. All four L-(alpha Me)Val residues prefer phi, psi angles in the right-handed helical region of the conformational map. The results indicate that: (i) the (alpha Me)Val residue is a strong type-I/III beta-turn and helix former, and (ii) the relationship between (alpha Me)Val chirality and helix screw sense is the same as that of C alpha-monosubstituted protein amino-acids. The implications for the use of the (alpha Me)Val residue in designing conformationally constrained analogues of bioactive peptides are briefly discussed.
Valle
G
G
Biopolymer Research Centre, C.N.R., Department of Organic Chemistry, University of Padova, Italy.
Crisma
M
M
Toniolo
C
C
Polinelli
S
S
Boesten
W H
WH
Schoemaker
H E
HE
Meijer
E M
EM
Kamphuis
J
J
D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D014961:X-Ray Diffraction
D010455:Peptides; D005998:Glycine