Molecular Design and Structure-Function of Ion Transfer Peptides : Ionophore and Extracellular Matrix Peptide with Metal Ion Binding Properties.

点击翻译按钮获取中文摘要

In the recent years we have efficiently used the CD spectroscopy methodology to perform original experiments relating the structure-function of a group of biologically active peptides.Aib (a-aminoisobutyric acid) analogues of the antibiotic transmembrane ion-channel peptide, linear gramicidin, have been synthesized and their reduced antimicrobial activity was attributed to the change of structure determined by CD spectroscopy (M.Jelokhani-Niaraki et al., J.Chem.Soc.Perkin Trans.2,1187-1193 (1992) ). In further experiments, the CD spectra of Aib analogues in aqueous, alcoholic and liposome environments were compared with the parent peptide gramicidin, and a structurally relevant transmembrane peptide pore-former, alamethicin. These data were used to design electrophysiological experiments to detect the pore-forming properties of the analogues (M.Kondo et al., Peptide Chemistry 1993,437-440 (1994) ). In more detailed experiments the helical structure of Aib analogues were determined unambiguously, and also their interhelical interaction in liposomes were suggested by using CD.By employing the CD data in combination with patch-clamp experiments a mechanism for interaction of gramicidin Aib analogues with phospholipid membranes, to interpret their pore-forming properties, was postulated [M.Jelokhani-Niaraki et al., J.Chem.Soc.Perkin Trans.2,1995 (to be published in the April issue), and Peptide Chemistry 1994,113-116 (1995) ].Other structural studies with CD are being performed on elastin and its polypeptide analogues, and their interaction with biological metal ions to investigate the phenomenon of self-assembly in this structural polypeptide (e.g.K.Okamoto et al., Peptide Chemistry 1993,297-300 (1994) ).Finally, it is our belief that CD spectroscopy, when combined with other methods (some of which are mentioned above), is a powerful tool for structural and functional studies of peptides and proteins, and their interactions with biological substances.