Effects of cation binding to hydrophobic helical peptides on orientation, aggregation, and ion-channel activity in phospholipid bilayer membranes

Abstract

~ ~~~ ~~~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.

Cation recognition by self-assembled monolayers of oriented helical peptides having a crown ether unit

“…This change is explained by complexation of the crown ether unit of LipoA16Cr with K ϩ , which stabilizes the helix conformation by favorable interaction of the positive charge with the negative pole of the macrodipole of LipoA16Cr. 20 In addition, the complexation of LipoA16Cr with K ϩ strengthens the molecular property of primary amphiphilicity. 21 The amphiphilic property should facilitate aggregation of the peptide, leading to increase in the magnitude of the negative Cotton effect around 222 nm.…”

“…These binding constants are larger than the binding constants of 18-crown-6 ether in aqueous solution, 26 because of favorable interaction between cations and the negative pole of LipoA16Cr as reported previously. 20 Furthermore, the less polar environment at the SAM surface may be favorable for the complexation. Reinhoudt et al explained similarly the large binding constants of a crown ether unit immobilized on alkanethiol SAMs.…”

Discriminating 310‐ from α‐helices: Vibrational and electronic CD and IR absorption study of related Aib‐containing oligopeptides

“…Peptide sequences containing high percentages of Aib (α‐aminoisobutyric acid or C α,α ‐dimethylglycine) are found as mixed 3 10 /α‐helical conformations in membrane‐active, linear peptaibol antibiotics with 10–20 residues such as alamethicin, antiamoebin, emerimicin, trichogin, trichorzianin, and zervamicin 13–15. The propensity for such peptides to form 3 10 ‐ or α‐helical structures is due to the steric constraints at the C α carbon, inherent to Aib 10, 16–22.…”

“…The propensity for such peptides to form 3 10 ‐ or α‐helical structures is due to the steric constraints at the C α carbon, inherent to Aib 10, 16–22. Aib‐based peptides have been proposed to exist as either equilibrium mixtures of interconverting 3 10 ‐ and α‐helical conformations or coupled 3 10 ‐ and α‐helical segments coexisting in the same molecule,16–24 depending on the main‐chain length, composition of amino acids, and exact sequence 10, 13, 21, 22, 25, 26…”

“…In infrared (IR) absorption, 3 10 ‐model helical peptides containing C α ‐tetra‐substituted α‐amino acids have an amide I band at higher frequencies (1658–1666 cm −1 )12, 28–30 than do α‐helices (1650–1658 cm −1 )31–33 in nonaqueous solutions. This small frequency shift of the amide I band cannot uniquely determine the conformation, as both distortions and irregularities in the helix,13, 34, 35 different types of residues,36 helix length,37, 38 solvent effects,39–42 and strain in the amide bond43 can result in higher (or lower) frequencies for either structure. Reports of a low amide I′ frequency for 3 10 ‐helical segments in proteins dissolved in D 2 O44 will be addressed in the Discussion section.…”