Tuning of the Supramolecular Helicity of Peptide-Based Gel Nanofibers.

Helical supramolecular architectures play important structural and functional roles in biological systems. The helicity of synthetic molecules can be tuned mainly by the chiral manipulation of the system. However, tuning of helicity by the achiral unit of the molecules is less studied. In this work, the helicity of naphthalimide-capped peptide-based gel nanofibers is tuned by the alteration of methylene units present in the achiral amino acid. The inversion of supramolecular helicity has been extensively studied by CD spectroscopy and morphological analysis. The density functional theory (DFT) study indicates that methylene spacers influence the orientation of π-π stacking interactions of naphthalimide units in the self-assembled structure that regulates the helicity. This work illustrates a new approach to tuning the supramolecular chirality of self-assembled biomaterials.

Single Amino-Acid Based Self-Assembled Biomaterials with Potent Antimicrobial Activity.

The design and development of soft biomaterials based on amino acid and short-peptide have gained much attention due to their potent biomedical applications. A slight alteration in the side-chain of single amino acid in a peptide or protein sequence has a huge impact on the structure and function. Phenylalanine is one of the most studied amino acids, which contains an aromatic phenyl group connected through a flexible -CH2 - unit. In this work, we have examined whether flexibility and aromatic functionality of phenylalanine (Phe) are important in gel formation of model gelator Fmoc-Phe-OH or not. To examine this hypothesis, we synthesized Fmoc-derivatives of three analogues unnatural amino acids including cyclohexylalanine, phenylglycine, and homophenylalanine; which are slightly varied from Phe. Interestingly, all these three new analogues formed hydrogels in phosphate buffer at pH 7.0 having different gelation efficacy and kinetics. This study suggests that the presence of aromatic side-chain and flexibility are not mandatory for the gelation of this model gelator. Newly synthesized unnatural amino acid derivatives have also exhibited promising antimicrobial activity towards gram-positive bacteria by inhibiting cellular oxygen consumption. We further determined the biocompatibility of these amino acid derivatives by using a hemolysis assay on human blood cells. Overall studies described the development of single amino acid-based new injectable biomaterials with improved antimicrobial activity by the slight alteration in the side-chain of amino acid.

Supramolecular Antiparallel ß-Sheet Formation by Tetrapeptides Based on Amyloid Sequence.

Self-assembly of short peptides has emerged as an interesting research field for a wide range of applications. Recently, several truncated fragments of long-chain peptides or proteins responsible for different neurodegenerative diseases were studied to understand whether they can mimic the property and function of native peptides or not. It was reported that such a kind of peptide adopts a ß-sheet structure in the disease state. It was observed that aromatic amino acid-rich peptide fragments possess a high tendency to adopt a ß-sheet conformation. In this article, we are first time reporting the crystal structure of two tetrapeptides: Boc-GAII-OMe (Peptide 1) and Boc-GGVV-OMe (Peptide 2), composed of aliphatic amino acids, and the sequences are similar to the Aß-peptide fragments Aß29-32 and Aß37-40 , respectively. In the solid-state, they are self-assembled in an antiparallel ß-sheet fashion. The peptide units are connected by the strong amide hydrogen-bonding (N-H···O) interactions. Apart from that, other noncovalent interactions are also present, which help to stabilize the cross-ß-sheet arrangement. Interestingly, in the crystal structure of Peptide 1, noncovalent C···C interaction between the electron-deficient carbonyl carbon, and the electron-rich sp3-carbon atom is observed, which is quite rare in the literature. The calculated torsion angles for these peptides are lying in the ß-sheet region of the Ramachandran plot. FT-IR studies also indicate the formation of an antiparallel ß-sheet structure in the solid-state. Circular dichroism of the peptides in the aqueous solution also suggests the presence of predominantly ß-sheet-like conformation in the aqueous solution. Under cross-polarized light, Congo Red stained both peptides showed green-gold color due to birefringence indicating their amyloidogenic nature. This result indicates that the short peptide composed of aliphatic amino acid is capable of forming a ß-sheet structure in the absence of aromatic amino acid and also can mimic the function of the native amyloid peptide.

Self-assembling behaviour of a modified aromatic amino acid in competitive medium.

Aromatic amino acid, specifically phenylalanine (Phe), is one of the most studied building blocks in peptide synthesis due to its importance in biology. It is reported in the literature that Phe-containing peptides have a high tendency to form different self-assembled materials due to efficient aromatic-aromatic interactions. In this article, we have tuned the supramolecular interactions of phenylalanine by making it electron-deficient upon introduction of the nitro group in the ring. The presence of the nitro group has a profound influence on the self-assembly process. It has been observed that 4-nitrophenylalanine (4NP) is a highly efficient gelator compared with the native phenylalanine in DMSO solvent in terms of minimum gelation concentration and it forms hydrogen bonding mediated crystals in water. The change of self-assembling patterns of 4NP in these solvents was studied using X-ray diffraction, UV-Vis spectroscopy, FE-SEM and other techniques. With the help of different experimental data and density functional theory (DFT), we have simulated the theoretical structure of 4NP in DMSO. The theoretical structure of 4NP in DMSO is different compared with that of crystals in water. We then studied the self-assembly process of 4NP in the mixed solvent of DMSO (polar aprotic) and water (polar protic). Different competitive non-covalent interactions of solvents as well as the ratio of the solvent mixture guide the final self-assembly state of 4NP.

Supramolecular Hydrogel from an Oxidized Byproduct of Tyrosine.

Herein we report for the first time the supramolecular hydrogelation of a derivative of 3-nitrotyrosine (3-NT), which is an oxidized byproduct of tyrosine, produced in the presence of reactive nitrogen species in the cell. The 9-fluorenylmethyloxycarbonyl (Fmoc) derivative of 3-NT, FNT, can form self-supported hydrogels at a wide range of pH values (4.5-8.5) in 50 mM phosphate buffer solutions. Hydrogels prepared at pH 7.0 are yellow, transparent, and thixotropic in nature. A yellow hydrogel was obtained by changing the pH from 4.5 to 8.5. Moreover, the gelation efficiency of the FNT gelator was enhanced by lowering the pH of the buffer solution. pH-Dependent self-assembly properties of the gelator were studied by using UV-vis, fluorescence, and circular dichroism spectroscopy and wide-angle X-ray diffraction techniques. Field-emission-scanning electron microscopy and transmission electron microscopy studies of the self-assembled FNT hydrogel showed a nanofibrillar network structure. Interestingly, the hydrogel showed injectable behavior at physiological pH. The low cytotoxicity value and high antimicrobial properties of the hydrogel indicated that it is a potential material for biomedical applications.