SYNTHETIC OLIGOMERS OF CONFORMATIONALLY RESTRICTED PEPTIDES AS MODELSFOR MEMBRANE CHANNELS

Helical peptaibols exhibit voltage dependence and form single-channel, multi-level conductance states in planar lipid bilayer. These are att ributed to aggregation of helical peptaibol monomers to form pores wit h different conductance states reflecting different numbers of monomer s in the pore. To gain better understanding of the molecular origin of voltage-dependent conductance, it would be reasonable to attempt to m odel aggregates of peptaibol monomers as fairly well defined dimers, t rimers, tetramers, etc. Our effort to synthesize an aggregate of defin ed structure is represented by the tetramer of 1-9 emerimicin. We used synthetic approach similar to TASP (Template Assembled Synthetic Prot eins). Boc-Lys(1-9 emerimicin)OH was used in solid phase synthesis for stepwise assembly of covalently bound 41 residue tetramer with the si multaneous formation of the tetralysine template part as a mouth of th e channel. This strategy is more conducive to controlling aggregate si ze and to monitoring purity. Further advantage is the possibility to o btain dimer, trimer, tetramer, etc. in one synthetic run. The strategy is being utilized for the synthesis of covalently bound oligomers of alamethicin as structurally defined models of voltage-gated channels.