Synthesis of a membrane-spanning lipophilic porphyrin with links to two alamethicin fragments on each face

Abstract

We have successfully synthesised α,β,α,β-tetrakis(2-amino-5-dodecyloxyphenyl)porphyrin in high yield. Its porphyrin precursor with nitro groups was synthesised without the use of high dilution. The dodecyloxy groups of this precursor increased its solubility. The yield of the desired α,β,α,β-atropisomer of the nitro-precursor could be enriched to 60% by treatment in hot toluene. The reduction of the nitro groups to the amino groups was carried out at room temperature. Thus, α,β,α,β-tetrakis(2-amino-5-dodecyloxyphenyl)porphyrin was synthesized under mild conditions on a multigram scale. This porphyrin possesses two amino groups and two dodecyloxy groups on each face of the porphyrin plane. It was combined with a fragment of alamethicin, a typical membrane peptide, to give a porphyrin–polypeptide hybrid, in which two hydrophobic polypeptides existed on each face of the porphyrin. This conjugate was successfully embedded into the lipid bilayer membrane. The resulting mixed vesicle showed the CD profile of a helical peptide. Thus, a membrane-penetrating columnar structure of α,β,α,β-tetrakis(2-peptidyl-5-dodecyloxyphenyl)porphyrin in the lipid bilayer membrane was suggested.