A Membrane Protein Model: Polypeptides with Four α-Helix Bundle Structure on 5,10,15,20-Tetrakis[2-(carboxymethoxy)phenyl]porphyrin

Abstract

A novel template for the polypeptide–porphyrin hybrid, 5,10,15,20-tetrakis[2-(ethoxycarbonylmethoxy)phenyl]porphyrin (2) was synthesized in 17% 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.

Self-Assembling of the Porphyrin-Linked Acyclic Penta- and Heptapeptides in Aqueous Trifluoroethanol

“…The amino acids near the porphyrins tune their enzymatic and photochemical reactivities, therefore, many groups have studied the conjugates of the porphyrins and the synthetic polypeptides . The representative motif of the conjugates is a four α-helix bundle structure of the polypeptides built on one face of the porphyrin . α-Helical polypeptides have been utilized to build porphyrin−polypeptide conjugates because of their defined structures and their synthetic developments .…”

Integration of a Reconstituted de Novo Synthesized Hemoprotein and Native Metalloproteins with Electrode Supports for Bioelectronic and Bioelectrocatalytic Applications

“…Extensive research efforts are directed to the de novo synthesis of proteins that provide a methodology of wide variability in biomimetic chemistry. , In particular, the approach to prepare synthetic proteins by antiparallel α-helix elements on a cyclic peptide provides an efficient strategy for the synthesis of predetermined structures . This method was successfully applied in tailoring a synthetic cytochrome b analogue by the assembly of four antiparallel helices containing two heme binding sites in the hydrophobic interior .…”

Supramolecular architectures of porphyrins on surfaces: The structural evolution from 1D to 2D to 3D to devices

“…Ferrocene-bridged trisporphyrin (14) self-assembles in solution to form macrocycles (15) ranging from dimers to decamers due to the coordination of the imidazolyl substituents with the Zn-centre of the adjacent porphyrin core (Fig. 7a) [88].…”

“…These distinctively multifunctional biomolecules are generally present as metallocomplexes where the four nitrogen atoms are coordinated to a metal atom such as Fe(III) or Mg(II). It is the combination of a rigid planar aromatic organic ligand and the redox properties of the metal which allows the natural tetrapyrrolic macrocycles to play a central role in electron transfer, oxygen transfer, and light-harvesting processes in metalloproteins [14][15][16][17][18]. Indeed, utilising such molecules to mimic biological events in nanotechnological devices would be of obvious benefit, however, due to the presence of two or more saturated carbon atoms in the macrocyclic scaffold, chlorins are not easily reproduced synthetically.…”

“…(a) Preparation scheme of a series of supramolecular macrocycles (15) using trimeric porphyrin precursor(14) via the coordination interaction through imidazolyl moieties and the Zn(II) metal centre of an adjacent porphyrin core. Covalent linking was performed by a ring-closing metathesis catalysed by a Grubbs-like catalyst of the allyl substituents at meso-positions.…”