Introduction and Objectives
1.8. Small peptide-based nanostructure
The speciality of the self-assembly process is the fabrication of various novel supramolecular structures. The concept of advancement of structural architecture comes from nature, as it produces various complex structures from amino acids, lipids, and nucleic acids in the biological system. Peptide nanostructures are essential due to their self-association efficiency, chemical variety, biocompatibility, capability for specific molecular recognition, and biodegradability.54-57 The fabrication of various vital nanostructures such as nanorods, nanobelts, nanofibrils, nanotapes, nanotubes, nanospheres, nano-ribbons, and gel has been developed by diverse self-assembled Structure, i.e., aromatic or aliphatic dipeptides58-59, cyclic peptides60, amphiphile peptides61, and surfactant-like peptides62. These nanostructures have essential applications in biotechnology and medicinal chemistry like ion channels63, drug delivery64, nano-
Chapter I Introduction
electronics65, nano-sensors66, tissue engineering67, and glucose transporters68. (Figure 1.14)
Figure 1.14. Various kinds of supramolecular strucrures and their applications
1.8.1. Di-peptides based self-assembly
Reches and Gazit reported that dipeptide Phe-Phe (FF), a central hydrophobic region of Aβ42, formed self-assembled peptide nanotubes. This nanotube has versatile applications in casting silver nanowire59, low molecular-mass organogel, electrochemical biosensing69, nanoforests70, and template for magnetic nanoparticles.71 Görbitz studied the structural insights of a series of unprotected hydrophobic di-peptides crystal, including FF peptides, which explain the mechanism of the formation of nanotubes.72 Zelenovskiy et al. reported that right and left-handed helix created by L-Phe-L-Phe and D-Phe-D-Phe peptides, respectively, and both formed nano-tubes structures.73
Yang and his group developed the formation of the twisted nano-ribbons structure by eight dipeptides containing L/D amino acid Phe and Phg.74 The handedness of nano- ribbons structure is governed by chirality and steric factor of Phe and Phg, respectively.
Chapter I Introduction
Ponnuswamy et al. discussed the crystalline properties of dipeptide Boc-VF-OMe (Aβ18- 19).75 Haldar et al. reported that this peptide formed amyloid-like fibrillar aggregates, and in solid-state, its exhibited supramolecular β-sheet and cross-β-sheet structure.50
They also reported that tyrosine-modified peptides (terminally protected FY, YF, YY) of Boc-FF-OMe (Aβ19-20) peptide-based inhibition of fibrils formation.51 Modified peptides formed microspheres structure compared to the fibrillar structure of protected FF.
SCXRD suggested that protected FF adopts an inverse γ-turn structure, whereas modified peptides formed a parallel β-sheet conformation.
Furthermore, they reported inhibition of fibril formation of modified peptide sequence of Boc-FL-OMe (AS6-7) by increasing peptide chain length and replacing aromatic-H with - OMe group.76 Different kinds of supramolecular arrangements were created by peptides sequence.
Görbitz et al. investigated the structural features of Boc-VV-OMe (Aβ39-40), which displayed a parallel β-sheet conformation.52 Our group reported crystallographic architecture of Boc-VV-OMe and Boc-IA-OMe (Aβ41-42); both formed parallel β-sheet structures in the solid-state but generated different morphology.53
Lorenzi et al. published the solid-state molecular packing of both side protected (Boc- for N-terminal, -OMe for C-terminal) dipeptides, containing L and D amino acids of Leu, Ile, allo-Ile.77
Later our group manifested diversity in nanostructure formation by terminally blocked (Boc- for N-terminal, -OMe for C-terminal) dipeptides bearing various combinations of L and D amino acids of Val and Ile.78 SC-XRD analysis suggested that peptides create different helix-like structure and hollow hexagonal tube-like architectures.
Moreover, our group discussed the diversity in conformation, morphology, and supramolecular packing of four terminally protected hydrophobic di-peptides bearing Ile, L/D Phe, and Phg, depending on chirality and side-chain of the amino acids.79
Pramanik et al. demonstrated the ω-amino acid bearing di-peptides such as Boc-β-Ala-m- ABA-OMe and Boc-γ-Abu-m-ABA-OMe (γ-Abu: γ -aminobutyric acid) self-assembled to β-sheet structure in solid-state.80 Both peptides formed amyloid-like fibrils structure, which has Congo red binding affinity.
Chapter I Introduction
Koley and Pramanik reported the formation of various nanostructures such as nanotubes, nanorods, nanovesicles, and nanofibrils by one hydrophobic amino acids (Phe, Tyr Trp, and Leu) and unnatural (o/m/p)-aminobenzoic acids bearing protected (Boc- for N- terminal, -OMe for C-terminal) di-peptides.81 Morphological variety depends on protecting group parameters and solvent polarity. Structural studies also discussed explaining the self-assembly mechanism.
Halder et al. reported that N-terminal protected three isomeric di-peptides of Boc-Phe- o/m/p-ABA-OH exhibited different morphology and N2-gas adsorption tendency.82 In the crystalline state, all formed a different kind of helical architecture.
Tai and his groups discussed the nano-structural diversity, i.e., nano-vesicles, nano- ribbons/fibrils, and nanotubes of Boc-m-ABA-Aib-OMe peptide in the presence of several physical and chemical stimuli.83 In a crystalline state, peptides form β-sheet layer- like structures, which explain the self-assembly mechanism for nano-vesicles formation.
Later, they studied the self-assembly of its reverse peptide sequence, i.e., Boc-Aib-m- ABA-OMe.84 Interestingly, the two peptides displayed distinctly different morphology and cell viability. Different kinds of molecular packing of those peptides explain the morphological heterogeneity.
1.8.2. Tri-peptides based self-assembly
Banerjee et al. developed the amyloid-like fibrils structure of VIA (Aβ39-40) peptide, and in solid-state, it formed an anti-parallel β-sheet arrangement.48 They also published GYE (Aβ9-11) hydrophilic tripeptide-based formation of amyloid-like fibrils and β-sheet structure.49
Adhikari et al. developed the chirality-dependent gelation behavior of conjugated ferrocene tripeptide FFA (Aβ19-21) and displayed various nanostructures such as nanorods and nanofibers.85
Haldar et al. developed organogel with sonication of nanofibers of Boc-VFF-OMe (Aβ18- 20) tripeptide.86 Marchesan et al. studied the unprotected VFF peptide and heterochiral isomers (D and L amino acid-containing peptides) based formation of hydrogel and various fibrous networks, where amino acids chirality plays the central role in the self-
Chapter I Introduction
assembly process.87,88 They also reported chirality-controlled hydrogel formation properties and fibrous network creation of unprotected FFV peptides and their isomers.89 Our group discussed the conformation, morphology, and supramolecular architecture of tri-peptide Boc-GFF-OMe and its analogous peptides by altering chirality and by incorporating unnatural amino acid, Phg.90