Effects of branched beta-carbon dehydro-residues on peptide conformations: syntheses, crystal structures and molecular conformations of two tetrapeptides: (a) N-(benzyloxycarbonyl)-DeltaVal-Leu-DeltaPhe-Leu-OCH3 and (b) N-(benzyloxycarbonyl)-DeltaIle-Ala-DeltaPhe-Ala-OCH3.
The roles of branched beta-carbon dehydro-residues in the design of peptide conformations have not been systematically explored so far. In order to determine the effects of branched beta-carbon dehydro-residues on the peptide conformations, two N-protected tetrapeptides containing new combinations of DeltaVal and DeltaPhe in (a) N-(benzyloxycarbonyl)-DeltaVal-Leu-DeltaPhe-Leu-OCH(3) and DeltaIle and DeltaPhe in (b) N-(benzyloxycarbonyl)-DeltaIle-Ala-DeltaPhe-Ala-OCH(3) were synthesized by solution procedure. The crystal structures of these peptides were determined by X-ray diffraction methods. Single crystals of both peptides were grown by slow evaporation method from their solutions in acetone-water mixtures (80 : 20) at 25 degrees C. The crystals of these peptides belong to the orthorhombic space group P2(1)2(1)2(1) with cell dimensions of a = 12.342(1) A, b = 15.659(1) A, c = 18.970(1) A for peptide (a) and a = 8.093(1) A, b = 15.791(1) A, c = 23.816(1) A for peptide (b) having Z = 4 in the unit cells of both peptides. The structures were refined by full-matrix least-squares procedure to R-factors of 0.076 and 0.052 respectively. Both peptides adopt the right-handed 3(10)-helical conformations stabilized by two intramolecular (i + 3-->i) hydrogen bonds between the CO of N-terminal benzyloxycarbonyl (Cbz) group and the NH of residue at position 3, and between the CO of residue at position 1 and NH of the residue at position 4. The two consecutive 10-membered rings formed by the hydrogen bonds have dihedral angles corresponding to the standard values for type III beta-turns. DeltaVal and DeltaIle in peptides (a) and (b) respectively are located at the (i + 1) position of the first beta-turn while DeltaPhe is located at the (i + 2) position of the second beta-turn. In the crystals, the molecules are linked head to tail by intermolecular hydrogen bonds to form long helical chains. The axes of helices are parallel to the b-axes while the neighbouring helices run in the opposite directions. The crystal packings are further stabilized by van der Waals forces between the columns of molecular packings.
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
V K
VK
Goel
R K
RK
Somvanshi
S
S
Dey
T P
TP
Singh
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D017433:Protein Structure, Secondary
D009842:Oligopeptides; D010455:Peptides; D010649:Phenylalanine