A Membrane Protein Model: Polypeptides with Four α-Helix Bundle Structure on 5,10,15,20-Tetrakisporphyrin

Article abstract of DOI:10.1246/bcsj.68.1989

A novel template for the polypeptide-porphyrin hybrid, 5,10,15,20-tetrakis<2-(ethoxycarbonylmethoxy)phenyl>porphyrin (2) was synthesized in 17percent yield.Four protected carboxyl groups are installed in 2 at the ortho-phenyl groups as the anchoring points, to which the N-termini of the polypeptides can be linked after the hydrolysis.Thus, 2 is a new analog of the porphyrin template tetrakis<2-(methoxycarbonyl)phenyl>porphyrin.The atropisomerization of 2 was much more rapid than that of tetrakis<2-(methoxycarbonyl)phenyl>porphyrin: At 353 K, 2 reached their equilibrium within 15 min.Such atropisomeric flexibility of 2 allows the self-organization of the α-helical peptide segments which are connected to 2.After the hydrolyses of the ethyl ester groups of 2, four α-helical 21-peptides, H-(-Gln-Leu-Leu-Gln-Ala-Leu-Ala-)3-NHCH2CH2OH were combined through the amide bonds to yield a new polypeptide-porphyrin hybrid (12).The polypeptide moieties of 12 showed typical α-helix profiles on circular dichroism measurements in methanol-water (3/1, v/v) and in Tris*HCl buffer solution.Thus, the four α-helix polypeptides are considered to fold into a bundle structure on the porphyrin template through the hydrophobic interaction.The circular dichroism spectrum of 12 in methanol showed an induced Cotton effect at the porphyrin region, and the CD band was symmetrically split.The hybrid (12) was also successfully incorporated into the egg yolk lecithin membrane almost quantitatively.When the molar ratio of egg yolk lecithin/12 was 500/1, the α-helix structure of the peptide segments in 12 was completely retained in the vesicles.