SYNOPSISAn apolar synthetic octapeptide, Boc-( Ala-Aib),-OMe, was crystallized in the triclinic space group P1 with cell dimensions a = 11.558 A, b = 11.643 A, c = 9.650 A, a = 120.220", 8 = 107.000", y = 90.430", V = 1055.889 A3, 2 = 1, CsrHsoOllNe.H20. The calculated crystal density was 1.217 g/cm3 and the absorption coefficient p was 6.1. All the intrahelical hydrogen bonds are of the 310 type, but the torsion angles, C # J and $, of Ala( 5) and Ala( 7) deviate from the standard values. The distortion of the 310-helix at the C-terminal half is due to accommodation of the bulky Boc group of an adjacent peptide in the packing. A water molecule is held between the N-terminal of one peptide and the C-terminal of the other. The oxygen atom of water forms hydrogen bonds with N( 1) -H and N( 2 ) -H, which are not involved in the intrahelical hydrogen bonds. The hydrogen atoms of water also formed hydrogen bonds with carbonyl oxygens of the adjacent peptide molecule. On the other hand, 'H-nmr analysis revealed that the octapeptide took an a-helical structure in a CD3CN solution. The longer peptides, Boc-( Ala-Aib)6-OMe and Boc-( Ala-Aib)8-OMe, were also shown to take an a-helical structure in a CD3CN solution. An a-helical conformation of the hexadecapeptide in the solid state was suggested by x-ray analysis of the crystalline structure. Thus, the critical length for transition from the 310-to a-helix of Boc-(Ala-Aib),-OMe is 8. 0 1993 John Wiley & Sons, Inc.

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~ ~~~ ~~~Effects of cation binding to the C-terminal of a-helical peptides on conformation, orientation, aggregation, and ion-channel activity in a phospholipid bilayer membrane have been studied. The hydrophobic helical peptides having a crown ether unit at the C-terminal region, Boc-[Ala-Aib],-Ala-Cr (Cr represents a benzo-18-crown-6 unit, n = 4,8), and an anthryl group at the N-terminal region as well, Boc-Ser(Ant)-[Ala-Aib].-Ala-Cr (Ant represents an anthrylmethyl group, n = 4,8),have been synthesized. The helix content of the peptides increased upon complexation with K + because of interaction of the negative pole of the helic macrodipole with the cation. The peptides were incorporated into a phospholipid bilayer membrane, and aggregated taking a transmembrane orientation. Boc-[Ala-Aib],-Ala-Cr showed an ion-channel-like activity in a bilayer membrane. The activity was higher than that of Boc-[Ala-Aib],-OMe, since the crown ether unit functions as a cation-binding site of the channel. The aggregation of the crown-peptides was promoted especially in the presence of Rb' and Cs+ due to formation of a sandwich-type crown/cation complex. For this reason, Boc-[Ala-Aib],-Ala-Cr showed a higher channel-like activity in the presence of Cs' than K'. On the other hand, Boc-[Ala-Aib],-Ala-Cr aggregated upon incorporation into a bilayer membrane, and showed an ion-channel-like activity. In any one of the peptides, the connection of a crown ether unit to the hydrophobic helical peptide augmented its channel-forming ability by facilitating aggregation with a transmembrane orientation.

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