Interactions of synthetic peptide analogs of the class A amphipathic helix with lipids. Evidence for the snorkel hypothesis.

Class A amphipathic helixes present in exchangeable plasma apolipoproteins are characterized by the location of positively charged amino acid residues at the non-polar-polar interface and negatively charged amino acid residues at the center of the polar face. The objectives of the present study were: (i) to investigate the role of hydrocarbon side chain length of the interfacial positively charged amino acid residues in the lipid affinity of class A amphipathic helixes, and (ii) to investigate the importance of the nature of interfacial charge in the lipid affinity of class A amphipathic helixes. Toward this end, lipid interactions of the following two analogs of the class A amphipathic helix, Ac-18A-NH2 (acetyl-Asp-Trp-Leu-Lys-Ala-Phe-Tyr- Asp-Lys-Val-Ala-Glu-Lys-Leu-Lys-Glu-Ala-Phe-NH2), and Ac-18A(Lys > Haa)-NH2 (acetyl-Asp-Trp-Leu-Haa-Ala-Phe-Tyr-Asp-Haa-Val-Ala-Glu-Haa-Leu-Haa-Glu- Ala-Phe-NH2) (Haa = homoaminoalanine), were studied.