Molecular design of cyclic peptides containing a non-natural amino acid: novel synthetic approach to artificial ion channels

Abstract

Interested in the structure-function relationship of natural and synthetic peptides, we have designed, synthesized, and evaluated a series of functional peptides containing rigid non-natural amino acid moiety(ies) such as 3-aminobenzoic acid [1]. The resulting functional peptides are restricted conformationally and, if cyclic, are expected to form a central cavity. Indeed, we have recently shown that the cyclic peptides (1–4) with long acyl chains are smoothly incorporated into a bilayer membrane and function as single ion channels [2], The same synthetic strategy, though applicable to the preparation of cyclic peptides consist of different amino acid moieties with similar side chains, cannot be extended to the syntheses of more sophisticated cyclic peptides carrying, for example, peptide side chains. We wish now to propose an advanced, more versatile methodology for preparing a wide variety of functional cyclic peptides. Using this synthetic strategy, we actually synthesized two cyclic peptides (5 and 6 ) carrying cholate groups or long peptide chains, which are expected to exhibit some novel ionchannel properties upon incorporation into a membrane.