1.D.156. The Alpha-Aminoxy Acid Channel (AAAC) Family
Cyclic hexapeptide 2 (2) was prepared from linear hexapeptide 1 of alternating d- and l-alpha-aminoxy acids, and was found to adopt a C3 symmetric and bracelet-like conformation with consecutive eight-membered-ring hydrogen bonds (N-O turns) in nonpolar solvents, similar to that of valinomycin, a cyclodepsipeptide that binds cations selectively (Yang et al. 2002). However, 2 showed affinities for halide ions with selectivity following the order of Cl- > F- > Br-. The observed higher selectivity for Cl- (Ka = 11880/M) over F- (Ka = 30/M) in CD2Cl2 suggested that the selectivity of 2 for halide ions is mainly governed by the size complementarity rather than the hydrogen-bonding strength. Upon Cl- ion binding, the original bracelet-like conformation of 2 turned into a rather flat conformation with all six amide NHs pointing inward to form hydrogen bonds with Cl-.
Chemists have developed peptidomimetic foldamers, unnatural oligomeric molecules that fold into rigid and well-defined secondary structures, mimicking the structures and biological functions of these natural peptides. Li et al. 2008 designed peptidomimetic foldamers that give predictable, backbone-controlled secondary structures, irrespective of the nature of the side chains. α-aminoxy acid units were used to construct a synthetic Cl- channel that mediates the passage of Cl- ions across cell membranes (Li et al. 2008). Structural modifications of α-aminoxy peptides on both their intestinal absorption and their transport mechanisms have been reported ( ). Structural modifications of α-aminoxy peptides on both their intestinal absorption and their transport mechanisms have been reported (Ma et al. 2011).