title: Quantitative structure-activity relationships for sea anemone polypeptide toxins.
abstract: Sea anemone polypeptides vary considerably in their affinities for sodium channels occurring in different excitable cells. The amino acid sequence variation in a set of six sea anemone type I polypeptide toxins (46-49 residues long), was parameterized using descriptor scales z1, z2, and z3, derived from a large number of amino acid physicochemical properties. The pharmacological properties of the toxins were represented by the results from four bioassays on crab, mouse, and rat brain and from rat heart. By means of the descriptor scales and the multivariate data analytical method PLS (partial least squares projections to latent structures), it was possible to develop quantitative structure-activity relationships (QSAR). Using the QSARs derived from the set of six polypeptide toxins the pharmacological properties of two homologous sea anemone polypeptide toxins were predicted. Thus it is shown that QSARs may be formulated for relatively long bioactive polypeptides. The QSARs indicate that 11 different amino acid positions may be of importance, but that positions no. 5, 21, 28, 34, 37, and 40 were of main importance in modeling the relative toxicities of the six polypeptides.
authors.affiliation: Department of Organic Chemistry, University of Umeå, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Hellberg
authors.forename: W R
authors.initials: WR
authors.lastname: Kem
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D003386:Brachyura / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D003064:Cnidarian Venoms / Q000737:chemistry* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007928:Lethal Dose 50; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship
chemical_list: D003064:Cnidarian Venoms; D010455:Peptides