Conformations of peptide fragments comprising the amino-terminal, central, and carboxyl-terminal regions of a membrane-active polypeptide. Build-up of secondary structure in pardaxin

Abstract

The conformations of synthetic peptides of different lengths corresponding to the amino-terminal, central, and carboxyl-terminal regions of pardaxin (GFFALIPKIISSPLFKTLLSAVGSALSSSGEQE) have been studied by circular dichroism spectroscopy. The peptides GFFALIPKIISSPLF-OMe, GFFALIPKIISSPLFK-OMe corresponding to the amino-terminal region, as well as peptides KIISSPLFKTLLSAV and IISSPLFKTLLSAV corresponding to the central region of the toxin have a marked tendency to adopt helical conformation. Ordered conformation is also discernible in the 8- and 7-residue peptides GFFALIPK-OMe and IISSPLF-OMe. Peptides corresponding to the central segments KTLLSAV, LSAVGSAL, and the carboxyl-terminal segment SSSGEQE, however, exhibit very little secondary structure. The peptide segments that adopt ordered conformation show similar conformation when present in the entire toxin as suggested by proton magnetic resonance data (Zagorski, M. G., Norman, D. G., Barrow, C. J., Iwashita, T., Tachibana, K., and Patel, D. J. (1991) Biochemistry 30, 8009-8017). The observation that peptide segments corresponding to the amino-terminal and central regions of the toxin adopt ordered conformations compared to the carboxyl-terminal segment in isolation as well as in the toxin, indicates a role for these regions in initiating and maintaining ordered conformation of pardaxin.