THE SOLUTION STRUCTURE AND ACTIVITY OF CAERIN-1.1, AN ANTIMICROBIAL PEPTIDE FROM THE AUSTRALIAN GREEN TREE FROG, LITORIA-SPLENDIDA

Caerin 1.1 is one of the major antimicrobial peptides isolated from th e skin of the Australian green tree frog, Litoria splendida. Two-dimen sional H-1-H-1 and H-1-C-13 NMR spectroscopy in trifluoroethanol/ H2O (50:50, by vol.) have been used to assign the H-1 and C-13-NMR spectra of this 25-amino-acid peptide. From an examination of these data, and using distance geometry and molecular dynamics calculations, the solu tion conformation of caerin 1.1 has been determined. The peptide adopt s two well-defined helices from Leu2 to Lys11 and from Val17 to His24 separated by a region of less-defined helicity and greater flexibility . Overall, the peptide has a distinct amphipathic charge distribution. The solution structure of caerin 1.1 is compared with activity data a gainst a variety of micro-organisms for the parent peptide and some na turally occurring and synthetic variants of caerin 1.1. The structural and activity data are consistent with caerin 1.1 interacting with mem branes in a similar manner to other antimicrobial peptides, i.e. via a carpet like mechanism whereby the individual peptides aggregate in a helical manner and orient themselves parallel to the membrane in a she et-like arrangement [Shai. Y. (1995) Trends Biochem. Sci. 20, 460-464] .