INDUCED CONFORMATIONAL STATES OF AMPHIPATHIC PEPTIDES IN AQUEOUS LIPID ENVIRONMENTS

Specific conformational effects have been reported for amphipathic mod el peptides upon binding of defined hydrophobic domains to nonpolar st ationary phases during reversed-phase high performance liquid chromato graphy (RP-HPLC). Such induced conformations are found to be especiall y pronounced for peptides that are amphipathic in an cu-helical confor mation. Such induced amphipathic conformations resulted in substantial ly later elution than predicted using amino acid-based retention coeff icients. In the present study, the induced conformational behavior of model peptides observed during RP-HPLC was correlated with their secon dary structure as determined by circular dichroism (CD) spectroscopy i n both aqueous solution and C-18-mimetic environments. The experimenta l retention times of the peptides studied were found to correlate with their CD spectra in the presence of lipids, whereas a poor correlatio n was observed with their CD spectra in the presence of trifluoroethan ol. A new approach was developed to evaluate the induction of secondar y structure in peptides due to interactions al aqueous/lipid interface s, which involves the measurement of the CD ellipticities of peptides bound to a set of C-18-coated quartz plates. An excellent correlation was found in this environment between the RP-HPLC retention times and CD ellipticities of the bound peptides.