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

Abstract

The conjugates of porphyrin with links to the acyclic penta- and heptapeptides were synthesized to mimic natural multiple porphyrin systems. The linear penta- and heptapeptide with hydrophilic/hydrophobic alternative sequences took a random structure in aqueous trifluoroethanol (TFE). However, these polypeptides took a beta-sheet structure in the same solvent when the N-terminal Cys linked to the porphyrin, suggesting that the conjugates self-assembled via the intermolecular hydrophobic interaction between the porphyrins. The circular dichroism (CD) spectra, UV/vis spectra, size exclusion chromatography (SEC), and (1)H NMR spectroscopy supported the self-assembling. In the self-assembled structure of the pentapeptide linking porphyrin at the p-phenyl position (9), the porphyrins were involved in two porphyrin-porphyrin interactions, i.e., the side-by-side interaction between the neighboring polypeptide chains and the face-to-face interaction between the first and the third peptide chains. The CD spectra of 9 showed two sets of Cotton effects probably arising from these two interactions. The UV/vis spectra also supported the above interpretation, showing multiple absorptions in the longwave and shortwave shifted regions. The SEC analyses showed the assembled structure of the conjugates. The (1)H NMR signals of the porphyrin rings of 9 were hardly observed in D(2)O-CD(3)OD because of the shortened spin-spin relaxation time T(2)().

Peptide-Tetrapyrrole Supramolecular Self-Assemblies: State of the Art

“…The first study of a peptide-porphyrin supramolecular self-assembly was reported in 2001 by Arai et al, who showed that conjugates 24a,b and 25 can adopt β-sheet assemblies in aqueous trifluoroethanol [74]. A follow-up study indicated that this behavior is promoted by the hydrophobic effect between neighboring porphyrins, as, under the same conditions, the free peptides are too short to fold in a β-sheet [75]. The peculiar CD and UV/Vis spectra of conjugate 24a suggest complex interactions between tetrapyrrole rings that stabilize the architecture.…”

Synthesis and Applications of Porphyrin-Biomacromolecule Conjugates

“…(E) Synthetic scheme for the preparation of peptideporphyrin conjugate using the bromoacetamide-cysteine reaction. (Arai et al, 2003). PpIX-Y113WF conjugate.…”

“…A complementary reaction that can be used to link porphyrinoids to cysteine residues of peptides is the thiol-haloacetamide ligation. In particular, bromo- and iodo-acetamides have been used as electrophilic sites ( Chaloin et al, 2001 ; Arai et al, 2003 ) with the thiol serving as a nucleophile. Since the thiol on cysteine is more nucleophilic than hydroxyl and amino side-chains on other amino acids, this reaction is selective for cysteine ligation ( Giuntini et al, 2011 ).…”

“…However, upon conjugation with the porphyrin at the N-terminal cysteine, the pentapeptide assembles into a β-sheet structure due to porphyrin-based pi-stacking. This tendency to form a β-sheet structure is interesting due to its resemblance to natural porphyrin self-assemblies ( Chaloin et al, 2001 ; Arai et al, 2003 ). The preparation of the bromoacetamide linked porphyrin partner involved first the synthesis of mono-nitro porphyrin using a modified Lindsey method followed by reduction ( via SnCl 2 ) to afford aniline containing porphyrin.…”

“…(D) Bioconjugation of maleimide functionalized porphyrin derivative with a thiol tethered CPP(Dondi et al, 2016). (E) Synthetic scheme for the preparation of peptideporphyrin conjugate using the bromoacetamide-cysteine reaction (Arai et al, 2003)…”