A novel D-leucine-containing Conus peptide: diverse conformational dynamics in the contryphan family

A Conus peptide family (the contryphans) is noteworthy because of the prese nce of a post-translationally modified D-amino acid in all members of the f amily. A new contryphan peptide, Leu-contryphan-P, was isolated from the ve nom of Conus purpurascens; the sequence of this peptide is: Gly-Cys-Val-D-Leu-Leu-Pro-Trp-Cys-OH This is the first known occurrence of D-leucine in a Conus peptide. The dis covery of Leu-contryphan-P suggests that there may be branches of the contr yphan peptide family that diverge much more in sequence than previously ant icipated. Several natural contryphans provide dramatic examples of intercon version between multiple conformational states in small constrained peptide s. The contryphans that have 4-trans-hydroxyproline and D-tryptophan in pos itions 3 and 4, respectively, exhibit two peaks under reverse-phase HPLC co nditions, indicating interconversion between two discrete conformations. Ho wever, [L-Trp(4)]contryphan-Sm (with L-Trp substituted for D-Trp) exhibits a single, broad peak that elutes later than the natural peptide, suggesting that D-Trp stabilizes a conformation in which hydrophobic residues are bur ied. Leu-contryphan-P which has valine and D-leucine instead of 4-trans-hyd roxyproline and D-tryptophan shows only a single peak that elutes much late r than the other contryphans.