Search Results (9)

The effects of proline co-solvent on helix folding are explored through the single discrete coordinate of the number of helical hydrogen bonds. The analysis is based on multi-microsecond length molecular dynamics simulations of alanine-based helix-forming peptides, (ALA)n, of length n = 4, 8, 15 and 21 residues, in an aqueous solution with 2 M concentration of proline. The effects of addition of proline on the free energy landscape for helix folding were analyzed using the graph-based Dijkstra algorithm, Optimal Dimensionality Reduction kinetic coarse graining, committor functions, as well as through the diffusion of the helix boundary. Viewed at a sufficiently long time-scale, helix folding in the coarse-grained hydrogen bond space follows a consecutive mechanism, with well-defined initiation and propagation phases, and an interesting set of intermediates. Proline addition slows down the folding relaxation of all four peptides, increases helix content and induces subtle mechanistic changes compared to pure water solvation. A general trend is for transition state shift towards earlier stages of folding in proline relative to water. For ALA5 and ALA8 direct folding is dominant. In ALA8 and ALA15 multiple pathways appear possible. For ALA21 a simple mechanism emerges, with a single path from helix to coil through a set of intermediates. Overall, this work provides new insights into effects of proline co-solvent on helix folding, complementary to more standard approaches based on three-dimensional molecular structures. Full article

The choline prolinate ([Ch][Pro]) as a hydrogen bond acceptor and ethylene glycol (EG) as a hydrogen bond donor are both used to synthesize the deep eutectic solvents (DESs) [Ch][Pro]-EG to capture CO₂. The CO₂ capacity of [Ch][Pro]-EG is determined, and the nuclear magnetic resonance (NMR) and infrared (IR) spectrum are used to investigate the CO₂ capture mechanism. The results indicate that CO₂ reacts with both the amino group of [Pro]⁻ anion and the hydroxyl group of EG, and the mechanism found in this work is different from that reported in the literature for the [Ch][Pro]-EG DESs. Full article

The objective of this study was to obtain co-amorphous systems of poorly soluble sinapic acid using amino acids as co-formers. In order to assess the probability of the interaction of amino acids, namely, arginine, histidine, lysine, tryptophan, and proline, selected as co-formers in the amorphization of sinapic acid, in silico studies were carried out. Sinapic acid systems with amino acids in a molar ratio of 1:1 and 1:2 were obtained using ball milling, solvent evaporation, and freeze drying techniques. X-ray powder diffraction results confirmed the loss of crystallinity of sinapic acid and lysine, regardless of the amorphization technique used, while remaining co-formers produced mixed results. Fourier-transform infrared spectroscopy analyses revealed that the co-amorphous sinapic acid systems were stabilized through the creation of intermolecular interactions, particularly hydrogen bonds, and the potential formation of salt. Lysine was selected as the most appropriate co-former to obtain co-amorphous systems of sinapic acid, which inhibited the recrystallization of sinapic acid for a period of six weeks in 30 °C and 50 °C. Obtained co-amorphous systems demonstrated an enhancement in dissolution rate over pure sinapic acid. A solubility study revealed a 12.9-fold improvement in sinapic acid solubility after introducing it into the co-amorphous systems. Moreover, a 2.2-fold and 1.3-fold improvement in antioxidant activity of sinapic acid was observed with respect to the ability to neutralize the 2,2-diphenyl-1-picrylhydrazyl radical and to reduce copper ions, respectively. Full article

Co-crystallization experiments of 4-halophenylboronic acid with several pharmaceutical compounds (including aciclovir, caffeine, nitrofurazone, and proline) produced several new molecular complexes. The experiments involved varying the solvent and the molar ratio of boronic acid to a pharmaceutical compound (e.g., 1:1, 2:1, 1:2). The screening process for new crystal phases revealed that the formation of the different molecular complexes was strongly influenced by the molar ratio and the presence or absence of water in the solvent. The new molecular crystals were characterized through single crystal X-ray diffraction and differential scanning calorimetry (DSC) analyses. The single crystal analyses of the molecular complexes revealed an unexpected variety in the hydrogen bonding network interactions that can be produced by the –B(OH)₂ motif. Full article

Beef bones contain a gelatin component that can be further extracted. This extraction process requires the right solvent to produce good yield and quality. Gelatin has multifunctional properties, namely biodegradable, biocompatible and non-toxic. This is because it is a natural ingredient that contains high amino acids. The most dominant amino acid content as a parameter for determining the quality of gelatin is proline, glycine, and hydroxyproline. The purpose of this study was to study the effect of the solvent used as a medium for soaking cow bones to be converted into gelatin. The solvent variations used include NaOH, HCl, H₂SO₄, CH₃COOH, and NaHCO₂. The concentration variations are 4, 5, 6, 7, 8 (%). This research method includes the preparation of cow bone samples, fat removal, mineral removal, soaking for 7 days, and extraction. The extraction process was carried out with variations times of 4 h and 6 h. The results of the study showed that the highest yield value was with 5% HCl solvent with 4 h extraction time of 26.5% with 8.67% water content, 0.9% ash content, pH 4.64, and viscosity 3.19 cP (p < 0.05). A good isoelectric point is produced when using an acidic solvent, which is between 5.3–5.8. The cross-linking of gelatin with chitosan, glutaraldehyde, and glucose was successfully carried out with the FTIR absorption indicator at a wavelength of 3200 cm⁻¹, which indicates the presence of hydrogen bonds, 1022 cm⁻¹, which indicates the breakdown of aldehyde bonds in glutaraldehyde compounds into C-O bonds. According to the microbial test, when gelatin is combined with chitosan, there will be an increase in the microbial inhibition zone. This shows that the development of gelatin materials is very prospective and promising. Full article

Spike protein of SARS-CoV-2 contains a single-span transmembrane (TM) domain and plays roles in receptor binding, viral attachment and viral entry to the host cells. The TM domain of spike protein is critical for viral infectivity. Herein, the TM domain of spike protein of SARS-CoV-2 was reconstituted in detergent micelles and subjected to structural analysis using solution NMR spectroscopy. The results demonstrate that the TM domain of the protein forms a helical structure in detergent micelles. An unstructured linker is identified between the TM helix and heptapeptide repeat 2 region. The linker is due to the proline residue at position 1213. Side chains of the three tryptophan residues preceding to and within the TM helix important for the function of S-protein might adopt multiple conformations which may be critical for their function. The side chain of W1212 was shown to be exposed to solvent and the side chains of residues W1214 and W1217 are buried in micelles. Relaxation study shows that the TM helix is rigid in solution while several residues have exchanges. The secondary structure and dynamics of the TM domain in this study provide insights into the function of the TM domain of spike protein. Full article

Co-crystals are one of the most popular ways to modify the physicochemical properties of active pharmaceutical ingredients (API) without changing pharmacological activity through non-covalent interactions with one or more co-formers. A “green method” has recently prompted many researchers to develop solvent-free techniques or minimize solvents for arranging the eco-friendlier process of co-crystallization. Researchers have also been looking for less-risk co-formers that produce the desired API’s physicochemical properties. This review purposed to collect the report studies of amino acids as the safe co-former and explored their advantages. Structurally, amino acids are promising co-former candidates as they have functional groups that can form hydrogen bonds and increase stability through zwitterionic moieties, which support strong interactions. The co-crystals and deep eutectic solvent yielded from this natural compound have been proven to improve pharmaceutical performance. For example, l-glutamine could reduce the side effects of mesalamine through an acid-base stabilizing effect in the gastrointestinal fluid. In addition, some amino acids, especially l-proline, enhances API’s solubility and absorption in its natural deep eutectic solvent and co-crystals systems. Moreover, some ionic co-crystals of amino acids have also been designed to increase chiral resolution. Therefore, amino acids are safe potential co-formers, which are suitable for improving the physicochemical properties of API and prospective to be developed further in the dosage formula and solid-state syntheses. Full article

Supramolecular chirality is one of the most important issues in different branches of science and technology, as stereoselective molecular recognition, catalysis, and sensors. In this paper, we report on the self-assembly of amphiphilic porphyrin derivatives possessing a chiral information on the periphery of the macrocycle (i.e., D- or L-proline moieties), in the presence of chiral amines as co-solute, such as chiral benzylamine derivatives. The aggregation process, steered by hydrophobic effect, has been studied in aqueous solvent mixtures by combined spectroscopic and topographic techniques. The results obtained pointed out a dramatic effect of these ligands on the morphology and on the supramolecular chirality of the final self-assembled structures. Scanning electron microscopy topography, as well as fluorescence microscopy studies revealed the formation of rod-like structures of micrometric size, different from the fractal structures formerly observed when the self-assembly process is carried out in the absence of chiral amine co-solutes. On the other hand, comparative experiments with an achiral porphyrin analogue strongly suggested that the presence of the prolinate moiety is mandatory for the achievement of the observed highly organized suprastructures. The results obtained would be of importance for unraveling the intimate mechanisms operating in the selection of the homochirality, and for the preparation of sensitive materials for the detection of chiral analytes, with tunable stereoselectivity and morphology. Full article

The aim of this study was to investigate the effects of various stabilizers on the encapsulation efficiency and release of exenatide-loaded PLGA (poly(lactic-co-glycolic acid)) microspheres prepared by the water-in-oil-in-water (W/O/W) solvent evaporation (SE) method. It was shown that the stabilizers affected exenatide stability in aqueous solutions, at water/dichloromethane interfaces, on PLGA surfaces, or during freeze-thawing and freeze-drying procedures. Sucrose predominantly reduces instability generated during freeze-thawing and freeze-drying. Phenylalanine prevents the destabilization at the water–dichloromethane (DCM) interface through decreased adsorption. Poloxamer 188 enhances stability in aqueous solutions and prevents adsorption to PLGA. Proline and lysine decrease adsorption on PLGA surfaces. Fourier transform infra-red spectroscopy (FT-IR) was used to find the molecular interaction of additives with exenatide or PLGA. Additives used in stability assessments were then added stepwise into the inner or outer water phase of the W/O/W double emulsion, and exenatide-loaded microspheres were prepared using the solvent evaporation method. The effect of each stabilizer on the encapsulation efficiency and release behavior of microspheres correlated well with the stability assessment results, except for the negative effect of poloxamer 188. Particle size analysis using laser diffractometry, scanning electron microscopy (SEM), water vapor sorption analysis, differential scanning calorimetry (DSC), and circular dichroism (CD) spectroscopy were also employed to characterize the prepared exenatide-loaded PLGA microsphere. This study demonstrated that an adequate formulation can be obtained by the study about the effect of stabilizers on peptide stability at the preformulation step. In addition, it can help to overcome various problems that can cause the destabilization of a peptide during the microsphere-manufacturing process and sustained drug release. Full article