Studies of synthetic helical peptides using circular dichroism and nuclear magnetic resonance.
We have designed a set of 17-residue synthetic peptides to be monomeric helices in aqueous solution. Circular dichrosim experiments indicate the presence of helical structure in aqueous solution at low temperature and low pH. The two-dimensional nuclear magnetic resonance results for one of the peptides show a segment of ten residues which clearly meets all of the criteria for the existence of helical structure at both 5 degrees C and 15 degrees C. The first four residues of the peptide are in a largely extended conformation. Calculations suggest that residues 5 through 14 are significantly helical at 5 degrees C. When the temperature is increased, circular dichroism spectra indicate that the helical content decreases. At 15 degrees C, the 3JN alpha coupling constants increase in the helical region, indicating an increase in motion or conformational averaging in the helical segment. None of the peptides has pH titration behavior consistent with salt bridge stabilization of helical conformation. Our data lend themselves to interpretation with the helix dipole model and specific side-chain interactions. When the N and C termini charges are removed the helical content of the peptides increases. The amount of helicity increases as the pH is lowered, due to the ionization of His16. Much of the helical stabilization appears to be due to a specific side-chain interaction between His16 and Tyr12.
Bradley
E K
EK
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143.
Thomason
J F
JF
Cohen
F E
FE
Kosen
P A
PA
Kuntz
I D
ID
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation
D010455:Peptides