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.
Biopolymer Research Centre, C.N.R., Department of Organic Chemistry, University of Padova, Italy.
G
G
Valle
M
M
Crisma
C
C
Toniolo
S
S
Polinelli
W H
WH
Boesten
H E
HE
Schoemaker
E M
EM
Meijer
J
J
Kamphuis
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