IR spectroscopy of isotope-labeled helical peptides: Probing the effect ofN-acetylation on helix stability

The effect of N-acetylation on the conformation of alanine-rich helical pep tides is examined using isotope-edited Fourier transform infrared (FTIR) sp ectroscopy. A series of peptides with sequence AA(AAKAA)(3)AAY has been pre pared; each peptide incorporates four C-13-labeled alanines. These peptides have two amide I' bands in their FTIR spectra: one corresponding to the C- 12 amino acids. and one assigned to the C-13 amino acids. The intensity and frequency of the C-13 amide I' band varies systematically with the positio n of the labels in the sequence and the presence or absence of an N-acetyl capping group. The intensity of the C-13 amide I' band correlates with heli x stability at the labeled residues as predicted by thermodynamic models of the helix-coil transition. These results suggest that FTIR spectroscopy co mbined with specific isotope labeling can be used to dissect the conformati on of helical peptides at the residue level. (C) 2000 John Wiley & Sons, In c.