Conformational effects of C(alpha,alpha)-dipropargylglycine as a constrained residue.
A useful synthon to approach artificial phenylalanyl peptides in a [2 + 2 + 2] cycloaddition reaction, C(alpha,alpha)-dipropargylglycine (Dprg) is examined for its conformational preferences as a constrained residue. Crystal structure analysis and preliminary NMR results establish possible preference of the residue for folded (alpha) rather than extended (beta) region of the straight phi,psi conformational space. Boc-Dprg-L-Leu-OMe (1) displays two molecular conformations within the same crystallographic asymmetric unit, with Dprg in the alpha(R) or alpha(L) conformation, participating in a type I beta-turn or an alpha(L)-alpha(R)-type fold, in which Leu(2) assumes the alpha(R) conformation stereochemically favored for an L-chiral residue. Boc-Dprg-D-Val-L-Leu-OMe (2) displays a type I' beta-turn conformation in crystal, with both Dprg(1) and D-Val(2) assuming the alpha(L) conformation stereochemically favored for a D-chiral residue, with 4 --> 1 type hydrogen bond linking L-Leu(3) NH with Boc CO. NMR analysis using temperature variation, solvent titration, and a spin probe study suggests a fully solvent-exposed nature of Dprg NH, ruling out a fully extended C(5)-type conformation for this residue, and solvent sequestered nature of L-Leu(3) NH, suggesting possibility of a beta-turn due to Dprg assuming a folded conformation.
Damodharan
L
L
Department of Crystallography and Biophysics, University of Madras, Chennai-600 025, India.
Mohanraja
K
K
Kotha
S
S
Durani
S
S
Pattabhi
V
V
D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry*; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry*; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry*; D011487:Protein Conformation; D014961:X-Ray Diffraction
C438365:C(alpha,alpha)-dipropargylglycine; D004151:Dipeptides; D009842:Oligopeptides; D010649:Phenylalanine; D005998:Glycine