A series of peptides with a long fatty acyl chain covalently attached to the C-terminal part and a free amine (-NH) group at the N-terminus have been designed so that these molecules can be assembled in aqueous medium by using various noncovalent interactions. Five different peptide amphiphiles with a general chemical formula [HN-(CH)CONH-Phe-CONHC (n = 1-5, C = dodecylamine)] have been synthesized, characterized, and examined for self-assembly and hydrogelation. All of these molecules [P1 (n = 1), P2 (n = 2), P3 (n = 3), P4 (n = 4), P5 (n = 5)] form thermoresponsive hydrogels in water (pH 6.6) with a nanofibrillar network structure. Interestingly, the hydrogels obtained from compounds P4 and P5 exhibit potential antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli). Dose-dependent cell-viability studies using MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) by taking human lung carcinoma (A549) cells vividly demonstrates the noncytotoxic nature of these gelator molecules in vitro. Hemolytic studies show nonsignificant or little hemolysis of human erythrocyte cells at the minimum inhibitory concentration (MIC) of these tested bacteria. Interestingly, it has been found that these antibacterial noncytotoxic hydrogels exhibit proteolytic resistance toward the enzymes proteinase K and chymotrypsin. Moreover, the gel strength and gel recovery time have been successfully modulated by varying the alkyl chain length of the N-terminally located amino acid residues. Similarly, the thermal stability of these hydrogels has been nicely tuned by altering the alkyl chain length of the N-terminally located amino acid residues. In the era of antibiotic-resistant strains of bacteria, the discovery of this new class of peptide-based antibacterial, proteolytically stable, injectable, and noncytotoxic soft materials holds future promise for the development of new antibiotics.

The self-assembled structure of toll-like receptor agonist lipopeptides containing the CSK4 peptide sequence is examined in aqueous solution. A remarkable dependence of morphology on the number of attached hexadecyl lipid chains is demonstrated, with spherical micelle structures for mono- and di-lipidated structures observed, but flexible wormlike micelles for the homologue containing three lipid chains. The distinct modes of assembly may have an important influence on the bioactivity of this class of lipopeptide.

Two-component fluorescent hydrogels have been discovered, containing the mixtures of naphthalene diimide (NDI)-conjugated peptide-functionalized bola-amphiphile and primary amines with long alkyl chains at physiological pH 7.46. The aggregation-induced enhanced emission associated with an NDI-appended peptide in aqueous medium is rare, as water is known to be a good quencher of fluorescence. In this study, an NDI-containing gelator peptide forms a highly fluorescent aggregate in aqueous medium. Absorption and emission spectroscopic techniques reveal the formation of J-aggregates among the chromophoric moieties in their aggregated state in aqueous medium. However, this NDI-containing peptide does not form any gel in aqueous medium. In the presence of the primary amines with long alkyl chains in the buffer solution, it forms two-component fluorescent hydrogels exhibiting bright yellow fluorescence under a UV lamp (365 nm). Probably, the acid-amine interaction between the amines and the bola-amphiphile triggers the gel formation, as evident from Fourier transform infrared data, indicating the presence of a carboxylate group (-COO) and an ammonium species (NH) in the coassembled two-component gel system. Low- and wide-angle powder X-ray diffraction and small-angle X-ray scattering further support the fact that the coassembled state in the gel form is produced by the supramolecular interaction between the NDI-based bola-amphiphile and the long-chain amines. Field-emission scanning electron microscopy and high-resolution transmission electron microscopy images reveal that the π-conjugated coassembled hydrogels exhibit nanofibrillar network morphologies. Interestingly, the coassembled hydrogels exhibit an enhanced fluorescence emission, excited-state lifetime, and quantum yield when compared with those of the NDI-containing amphiphile alone in its self-assembled state in aqueous medium. Moreover, the thermal stability and mechanical strength of these gels have been successfully tuned by varying the alkyl chain length of the corresponding amine. Moreover, these NDI-peptide-conjugated soft materials exhibit semiconducting behavior in their respective coassembled states. This holds future promise to use these peptide-appended NDI-based coassembled soft materials for applications in optoelectronic and other devices.

The cyclic lipopeptide Daptomycin, used as a treatment for infections where antimicrobial resistance is observed, is shown to self-assemble into spherical micelles above a critical aggregation concentration. Micelles are observed either in the absence or presence of CaCl2 , in contrast to claims in the literature that CaCl2 is required for micellization.

Amyloid fibrils are formed by a model surfactant-like peptide (Ala)10-(His)6 containing a hexa-histidine tag. This peptide undergoes a remarkable two-step self-assembly process with two distinct critical aggregation concentrations (cac's), probed by fluorescence techniques. A micromolar range cac is ascribed to the formation of prefibrillar structures, whereas a millimolar range cac is associated with the formation of well-defined but more compact fibrils. We examine the labeling of these model tagged amyloid fibrils using Ni-NTA functionalized gold nanoparticles (Nanogold). Successful labeling is demonstrated via electron microscopy imaging. The specificity of tagging does not disrupt the β-sheet structure of the peptide fibrils. Binding of fibrils and Nanogold is found to influence the circular dichroism associated with the gold nanoparticle plasmon absorption band. These results highlight a new approach to the fabrication of functionalized amyloid fibrils and the creation of peptide/nanoparticle hybrid materials.