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. 2024 Sep 18;15(41):16908-16916.
doi: 10.1039/d4sc04023f. Online ahead of print.

Designer pseudopeptides: autofluorescent polygonal tubes via Phe-zipper and triple helix

V Haridas  1   2 , Govind P Maurya  1 , Souvik Dutta  1
Affiliations

Designer pseudopeptides: autofluorescent polygonal tubes via Phe-zipper and triple helix

V Haridas et al. Chem Sci. .

Abstract

Chemists are increasingly turning to biology for inspiration to develop novel and superior synthetic materials. Here, we present an innovative peptide design strategy for tubular assembly. In this simple design, a phenylene urea unit is introduced as an aglet at the N-terminus of the peptide. When α-amino isobutyric acid (Aib) is the first residue and phenylalanine (Phe) is the second residue from the phenylene urea entity, it induces an edge-to-face π-π interaction resulting in a turn conformation. The peptides with a unique reverse turn conformation associate to form polygonal peptide tubes via a Phe-zipper arrangement, as evidenced by microscopic and single crystal X-ray studies. Ultra-microscopic imaging revealed that the tubular assembly is hexagonal, square, and triangular in shape. This hierarchical assembly reveals the interplay between π-π interactions and hydrogen bonding. In another design, pseudopeptide 5, wherein a Phe-Phe (FF) unit is linked to phenylene urea, formed polygonal tubes via a triple helical arrangement. Interestingly, the extension of this design to the bis-urea core resulted in vesicular assembly. These supramolecular polygonal tubes and vesicles showed autofluorescence, which allowed confocal imaging. The observed fluorescence is an additional advantage for applications in biological and medical sciences.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Chemical structures of the amino acid-based mono-urea compounds 1–5 and bis-urea compounds 6–9.
Fig. 2
Fig. 2. (a) Crystal structure of peptide 1 showing the turn conformation. Intramolecular edge-to-face π–π interaction is shown as green dotted lines, (b) CD spectrum of peptide 1 in acetonitrile, (c) space-filling model of aromatic rings showing the Phe–Phe zipper arrangement. The zoomed-in part shows the orientation of aromatic rings.
Fig. 3
Fig. 3. (a) Typical type I′ β-turn (PDB ID: 1KKO) and (b) typical type I β-turn (PDB ID: 2BK9). The green ribbon traces the backbone of protein. Overlayed images of (c) peptide 1 over a typical type I′ β-turn and (d) peptide 2 placed over typical type I β-turn. The numbering has been done considering each aromatic unit as one atom.
Fig. 4
Fig. 4. SEM images of 1 show (a) tubular assembly (indicated by red arrows), (b) intermediate stage of microtube formation (marked by red arrows) and (c) microtube structure. TEM images of 1 show (d) tubular assembly (indicated by red arrows) and (e) microtube structure (indicated by red arrows). AFM image of 1 shows (f) microtubular assembly and (g) schematic representation of self-assembly of 1 to a microtube.
Fig. 5
Fig. 5. FESEM images of 1 taken at an angle of 10° from the surface showing the open end of the microtubular assembly. The images reveal that tubular assembly is (a) triangular, square, and (b) hexagonal in shape. Zoomed images are shown in the insets (red arrows showing triangular tubes and yellow arrows showing square-shaped tubes); (c) FESEM images of 5 taken at an angle of 10° from the surface showing the open end of the microtubular assembly.
Fig. 6
Fig. 6. SEM images of (a) 2, (b) 4 and (c) 5 showing their tubular morphology, and SEM images of (d) 6, (e) 7 and (f) 8 showing their spherical morphology. The samples were prepared by dissolving 1 mg of respective compounds in 1 mL of ACN.
Fig. 7
Fig. 7. (a) Single crystal structure of compound 5, (b) left-handed helical arrangement of 5, and (c) the left-handed helical arrangement of (I) phenyl ring of phenylene urea, (II) middle phenyl unit (Phe1), (III) terminal phenyl unit (Phe2), and (IV) overlap of (I), (II) and (III) showing a triple helical arrangement.
Fig. 8
Fig. 8. Zoomed-in image of the triple helix formed by peptide 5 showing edge-to-face π–π interactions between the aromatic ring of the urea unit (colored in orange) and the phenyl ring of the second Phe-residue (Phe2) (colored in green).
Fig. 9
Fig. 9. Confocal images of compound 1 upon excitation at (a) 405 nm, (b) 488 nm, and (c) 560 nm. Confocal images of compound 7 upon excitation at (d) 405 nm, (e) 488 nm, and (f) 560 nm.
Fig. 10
Fig. 10. CD spectra of (a) 6, (b) 7 and (c) 8 alone and with H2PO4−, followed by addition of water.
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