Hybrid peptide hairpins containing alpha- and omega-amino acids: conformational analysis of decapeptides with unsubstituted beta-, gamma-, and delta-residues at positions 3 and 8.
The effects of inserting unsubstituted omega-amino acids into the strand segments of model beta-hairpin peptides was investigated by using four synthetic decapeptides, Boc-Leu-Val-Xxx-Val-D-Pro-Gly-Leu-Xxx-Val-Val-OMe: peptide 1 (Xxx=Gly), peptide 2 (Xxx=betaGly=betahGly=homoglycine, beta-glycine), peptide 3 (Xxx=gammaAbu=gamma-aminobutyric acid), peptide 4 (Xxx=deltaAva=delta-aminovaleric acid). 1H NMR studies (500 MHz, methanol) reveal several critical cross-strand NOEs, providing evidence for beta-hairpin conformations in peptides 2-4. In peptide 3, the NMR results support the formation of the nucleating turn, however, evidence for cross-strand registry is not detected. Single-crystal X-ray diffraction studies of peptide 3 reveal a beta-hairpin conformation for both molecules in the crystallographic asymmetric unit, stabilized by four cross-strand hydrogen bonds, with the gammaAbu residues accommodated within the strands. The D-Pro-Gly segment in both molecules (A,B) adopts a type II' beta-turn conformation. The circular dichroism spectrum for peptide 3 is characterized by a negative CD band at 229 nm, whereas for peptides 2 and 4, the negative band is centered at 225 nm, suggesting a correlation between the orientation of the amide units in the strand segments and the observed CD pattern.
Roy
Rituparna S
RS
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
Gopi
Hosahudya N
HN
Raghothama
Srinivasarao
S
Karle
Isabella L
IL
Balaram
Padmanabhan
P
D000596:Amino Acids / Q000737:chemistry*; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding
D000596:Amino Acids; D009842:Oligopeptides