Diverging conformations guide dipeptide self-assembly into crystals or hydrogels.

The prediction of dipeptide assembly into crystals or gels is challenging. This work reveals the diverging conformational landscape that guides self-organization towards different outcomes. In silico and experimental data enabled deciphering of the electronic circular dichroism (ECD) spectra of self-assembling dipeptides to reveal folded or extended conformers as key players.

A biocatalytic and thermoreversible hydrogel from a histidine-containing tripeptide.

We report the first histidine-containing self-assembling tripeptide devoid of capping groups that forms a thermoreversible hydrogel under physiological conditions and catalyses hydrolysis of an ester, providing a minimalist building block for functional soft materials.

Design of a hydrophobic tripeptide that self-assembles into amphiphilic superstructures forming a hydrogel biomaterial.

We report the rational design of a heterochiral hydrophobic tripeptide self-assembling into amphiphilic d-superstructures that yield a self-supportive hydrogel at physiological pH. The material endures cell culture conditions and sustains fibroblast proliferation. Tripeptide superstructures are thoroughly analysed by several techniques.

Under the lens: carbon nanotube and protein interaction at the nanoscale.

The combination of the very different chemical natures of carbon nanotubes (CNTs) and proteins gives rise to systems with unprecedented performance, thanks to a rich pool of very diverse chemical, electronic, catalytic and biological properties. Here we review recent advances in the field, including innovative and imaginative aspects from a nanoscale point of view. The tubular nature of CNTs allows for internal protein encapsulation, and also for their external coating by protein cages, affording bottom-up ordering of molecules in hierarchical structures. To achieve such complex systems it is imperative to master the intermolecular forces between CNTs and proteins, including geometry effects (e.g. CNT diameter and curvature) and how they translate into changes in the local environment (e.g. water entropy). The type of interaction between proteins and CNTs has important consequences for the preservation of their structure and, in turn, function. This key aspect cannot be neglected during the design of their conjugation, be it covalent, non-covalent, or based on a combination of both methods. The review concludes with a brief discussion of the very many applications intended for CNT-protein systems that go across various fields of science, from industrial biocatalysis to nanomedicine, from innovative materials to biotechnological tools in molecular biology research.

Higher and lower supramolecular orders for the design of self-assembled heterochiral tripeptide hydrogel biomaterials.

The self-assembly behaviour of the eight stereoisomers of Val-Phe-Phe tripeptides under physiological conditions is assessed by several spectroscopy and microscopy techniques. We report the first examples of self-organised hydrogels from tripeptides in the l-d-l or d-l-d configuration, besides the expected gels with the d-l-l or l-d-d configuration, thus widening the scope for using amino acid chirality as a tool to drive self-assembly. Importantly, the positions of d- and l-amino acids in the gelling tripeptides determine a higher or lower supramolecular order, which translates into macroscopic gels with different rheological properties and thermal behaviours. The more durable hydrogels perform well in cytotoxicity assays, and also as peptides in solution. An appropriate design of the chirality of self-assembling sequences thus allows for the fine-tuning of the properties of the gel biomaterials. In conclusion, this study adds key details of supramolecular organization that will assist in the ex novo design of assembling chiral small molecules for their use as biomaterials.

Chirality effects at each amino acid position on tripeptide self-assembly into hydrogel biomaterials.

Hydrogels formed by ultrashort peptides are emerging as cost-effective materials for cell culture. However, L-peptides are labile to proteases, while their D-isomers are thought to not support cell growth as well. In contrast, the self-assembly behaviour and biological performance of heterochiral peptides (i.e., made of both d and l amino acids) are largely unknown. In this study, we evaluate the effects of amino acid chirality on tripeptide self-assembly and hydrogelation at physiological pH, and cytocompatibility in fibroblast cell culture. A series of uncapped hydrophobic tripeptides with all combinations of d, l amino acids was prepared, tested for self-assembly under physiological conditions, and analysed by circular dichroism, FT-IR, cryo-TEM, AFM, and Thioflavin T fluorescence imaging. Amino acid chirality has a profound effect on the peptides' supramolecular behaviour. Only selected isomers form hydrogels, and of amyloid structure, as confirmed by rheology and XRD. Importantly, they are able to maintain the viability and proliferation of fibroblasts in vitro. This study identifies two heterochiral gels that perform well in cell culture and will assist in the design of innovative and cost-effective peptide gel biomaterials.

Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats.

The objective of this study was to determine the effect of eight 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-carboxyamidepyrazoles (TFDPs) on rat body temperature and baker's yeast-induced fever. TFDPs or vehicle (5% Tween 80 in 0.9% NaCl, 5 mL/kg) were injected subcutaneously and rectal temperature was measured as a function of time in 28-day-old male Wistar rats (N = 5-12 per group). Antipyretic activity was determined in feverish animals injected with baker's yeast (Saccharomyces cerevisiae suspension, 0.135 mg/kg, 10 mL/kg, ip). 3-Ethyl- and 3-propyl-TFDP (140 and 200 µmol/kg, respectively, 4 h after yeast injection) attenuated baker's yeast-induced fever by 61 and 82%, respectively. These two effective antipyretics were selected for subsequent analysis of putative mechanisms of action. We then determined the effects on cyclooxygenase-1 and -2 (COX-1 and COX-2) activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) oxidation in vitro, on tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels and on leukocyte counts in the washes of peritoneal cavities of rats injected with baker's yeast. While 3-ethyl- and 3-propyl-TFDP did not reduce baker's yeast-induced increases of IL-1ß or TNF-α levels, 3-ethyl-TFDP caused a 42% reduction in peritoneal leukocyte count. 3-Ethyl- and 3-propyl-TFDP did not alter COX-1 or COX-2 activities in vitro, but presented antioxidant activity in the DPPH assay with an IC50 of 39 mM (25-62) and 163 mM (136-196), respectively. The data indicate that mechanisms of action of these two novel antipyretic pyrazole derivatives do not involve the classic inhibition of the COX pathway or pyrogenic cytokine release.

Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats

The objective of this study was to determine the effect of eight 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-carboxyamidepyrazoles (TFDPs) on rat body temperature and baker’s yeast-induced fever. TFDPs or vehicle (5 percent Tween 80 in 0.9 percent NaCl, 5 mL/kg) were injected subcutaneously and rectal temperature was measured as a function of time in 28-day-old male Wistar rats (N = 5-12 per group). Antipyretic activity was determined in feverish animals injected with baker’s yeast (Saccharomyces cerevisiae suspension, 0.135 mg/kg, 10 mL/kg, ip). 3-Ethyl- and 3-propyl-TFDP (140 and 200 μmol/kg, respectively, 4 h after yeast injection) attenuated baker’s yeast-induced fever by 61 and 82 percent, respectively. These two effective antipyretics were selected for subsequent analysis of putative mechanisms of action. We then determined the effects on cyclooxygenase-1 and -2 (COX-1 and COX-2) activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) oxidation in vitro, on tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and on leukocyte counts in the washes of peritoneal cavities of rats injected with baker’s yeast. While 3-ethyl- and 3-propyl-TFDP did not reduce baker’s yeast-induced increases of IL-1β or TNF-α levels, 3-ethyl-TFDP caused a 42 percent reduction in peritoneal leukocyte count. 3-Ethyl- and 3-propyl-TFDP did not alter COX-1 or COX-2 activities in vitro, but presented antioxidant activity in the DPPH assay with an IC50 of 39 mM (25-62) and 163 mM (136-196), respectively. The data indicate that mechanisms of action of these two novel antipyretic pyrazole derivatives do not involve the classic inhibition of the COX pathway or pyrogenic cytokine release.