Design of Hollow Protein Nanoparticles with Modifiable Interior and Exterior Surfaces

Protein‐based nanoparticles hold promise for a broad range of applications. Here, we report the production of a uniform anionic hollow protein nanoparticle, designated TIP60, which spontaneously assembles from a designed fusion protein subunit based on the geometric features of polyhedra. We show that TIP60 tolerates mutation and both its interior and exterior surfaces can be chemically modified. Moreover, TIP60 forms larger structures upon the addition of a cationic protein. Therefore, TIP60 can be used as a modifiable nano‐building block for further molecular assembly.     

ASEDock-docking based on alpha spheres and excluded volumes

ASEDock is a novel docking program based on a shape similarity assessment between a concave portion (i.e., concavity) on a protein and the ligand. We have introduced two novel concepts into ASEDock. One is an ASE model, which is defined by the combination of alpha spheres generated at a concavity in a protein and the excluded volumes around the concavity. The other is an ASE score, which evaluates the shape similarity between the ligand and the ASE model. The ASE score selects and refines the initial pose by maximizing the overlap between the alpha spheres and the ligand, and minimizing the overlap between the excluded volume and the ligand. Because the ASE score makes good use of the Gaussian-type function for evaluating and optimizing the overlap between the ligand and the site model, it can pose a ligand onto the docking site relatively faster and more effectively than using potential energy functions. The posing stage through the use of the ASE score is followed by full atomistic energy minimization. Because the posing algorithm of ASEDock is free from any bias except for shape, it is a very robust docking method. A validation study using 59 high-quality X-ray structures of the complexes between drug-like molecules and the target proteins has demonstrated that ASEDock can faithfully reproduce experimentally determined docking modes of various druglike molecules in their target proteins. Almost 80% of the structures were reconstructed within the estimated experimental error. The success rate of approximately 98% was attained based on the docking criterion of the root-mean-square deviation (RMSD) of non-hydrogen atoms (< or = 2.0 A). The markedly high success of ASEDock in redocking experiments clearly indicates that the most important factor governing the docking process is shape complementarity.     

Trehalose and trehalose-based polymers for environmentally benign, biocompatible and bioactive materials

Trehalose is a non-reducing disaccharide that is found in many organisms but not in mammals. This sugar plays important roles in cryptobiosis of selaginella mosses, tardigrades (water bears), and other animals which revive with water from a state of suspended animation induced by desiccation. The interesting properties of trehalose are due to its unique symmetrical low-energy structure, wherein two glucose units are bonded face-to-face by 1-->1-glucoside links. The Hayashibara Co. Ltd., is credited for developing an inexpensive, environmentally benign and industrial-scale process for the enzymatic conversion of alpha-1,4-linked polyhexoses to alpha,alpha-D-trehalose, which made it easy to explore novel food, industrial, and medicinal uses for trehalose and its derivatives. Trehalosechemistry is a relatively new and emerging field, and polymers of trehalose derivatives appear environmentally benign, biocompatible, and biodegradable. The discriminating properties of trehalose are attributed to its structure, symmetry, solubility, kinetic and thermodynamic stability and versatility. While syntheses of trehalose-based polymer networks can be straightforward, syntheses and characterization of well defined linear polymers with tailored properties using trehalose-based monomers is challenging, and typically involves protection and deprotection of hydroxyl groups to attain desired structural, morphological, biological, and physical and chemical properties in the resulting products. In this review, we will overview known literature on trehalose's fascinating involvement in cryptobiology; highlight its applications in many fields; and then discuss methods we used to prepare new trehalose-based monomers and polymers and explain their properties.     

In situ Observation of Evolving H2 and Solid Electrolyte Interphase Development at Potassium Insertion Materials within Highly Concentrated Aqueous Electrolytes

The solid-electrolyte interphase (SEI) is key to stable, high voltage lithium-ion batteries (LIBs) as a protective barrier that prevents electrolyte decomposition. The SEI is thought to play a similar role in highly concentrated water-in-salt electrolytes (WISEs) for emerging aqueous batteries, but its properties remain unknown. In this work, we utilized advanced scanning electrochemical microscopy (SECM) and operando electrochemical mass spectrometry (OEMS) techniques to gain deeper insight into the SEI that occurs within highly concentrated WISEs. As a model, we focus on a 55 mol/kg K(FSA)_0.6(OTf)_0.4 electrolyte and a 3,4,9,10-perylenetetracarboxylic diimide negative electrode. For the first time, our work showed distinctly passivating structures with slow apparent electron transfer rates alike to the SEI found in LIBs. In situ analyses indicated stable passivating structures when PTCDI was stepped to low potentials (≈−1.3 V vs. Ag/AgCl). However, the observed SEI was discontinuous at the surface and H₂ evolution occurred as the electrode reached more extreme potentials. OEMS measurements further confirmed a shift in the evolution of detectable H₂ from −0.9 V to <−1.4 V vs. Ag/AgCl when changing from dilute to concentrated electrolytes. In all, our work shows a combined approach of traditional battery measurements with in situ analyses for improving characterization of other unknown SEI structures.     

Liposome modified with Mn-porphyrin complex can simultaneously induce antioxidative enzyme-like activity of both superoxide dismutase and peroxidase

An antioxidative liposome catalysis that mimics both superoxide dismutase (SOD) and peroxidase (POD) activities has been developed by using the liposomes modified with lipophilic Mn-(5,10,15,20-tetrakis[1-hexadecylpyridium-4-yl]-21H,23H-porphyrin) (Mn-HPyP). The SOD- and POD-like activities of the Mn-HPyP-modified liposome were first investigated by varying the type of phospholipid, such as 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC). Higher SOD-like activity was obtained in the case of DLPC and DMPC liposomes, in which the ligands were well-dispersed on the membrane in the liquid crystalline phase. The POD-like activity was maximal in the case of DMPC liposome, in which the Mn-HPyP complex was appropriately clustered on the membrane in the gel phase. On the basis of the above results, the co-induction of the SOD and POD activities to eliminate the superoxide and also hydrogen peroxide as a one-pot reaction was finally performed by using the Mn-HPyP-modified DMPC liposome, resulting in an increase in the efficiency of the elimination of both superoxide and hydrogen peroxide.     

Supervised scoring models with docked ligand conformations for structure-based virtual screening

Protein-ligand docking programs have been used to efficiently discover novel ligands for target proteins from large-scale compound databases. However, better scoring methods are needed. Generally, scoring functions are optimized by means of various techniques that affect their fitness for reproducing X-ray structures and protein-ligand binding affinities. However, these scoring functions do not always work well for all target proteins. A scoring function should be optimized for a target protein to enhance enrichment for structure-based virtual screening. To address this problem, we propose the supervised scoring model (SSM), which takes into account the protein-ligand binding process using docked ligand conformations with supervised learning for optimizing scoring functions against a target protein. SSM employs a rough linear correlation between binding free energy and the root mean square deviation of a native ligand for predicting binding energy. We applied SSM to the FlexX scoring function, that is, F-Score, with five different target proteins: thymidine kinase (TK), estrogen receptor (ER), acetylcholine esterase (AChE), phosphodiesterase 5 (PDE5), and peroxisome proliferator-activated receptor gamma (PPARgamma). For these five proteins, SSM always enhanced enrichment better than F-Score, exhibiting superior performance that was particularly remarkable for TK, AChE, and PPARgamma. We also demonstrated that SSM is especially good at enhancing enrichments of the top ranks of screened compounds, which is useful in practical drug screening.     

Preparation of rapidly disintegrating tablets containing itraconazole solid dispersions

The disintegratability of tablets prepared from two types of solid dispersions containing the water-soluble polymer TC-5 and the enteric polymer HP-55 as an excipient were compared. The disintegratability was better in the tablets of solid dispersions containing non-water-soluble HP-55 than those containing TC-5. In consideration of the dissolubility of solid dispersions containing HP-55, the mean diameter of the solid dispersion (coating powder) must be controlled to 120 microm or less, but as this markedly increases the adhesion/aggregation tendency of the particles (angle of repose: 47 degrees ), control of the adhesion/aggregation tendency emerged as another problem. Therefore, surface-modification was performed in a high-speed agitating granulator using 0.1% light anhydrous silicic acid as a surface modifier, and marked improvement in the flowability was observed. This made continuous tableting using a rotary tablet machine possible even with the poorly flowable solid dispersions. Also, in tableting of the solid dispersions, no recrystallization of amorphous itraconazole by the tableting pressure was observed, and the tablets maintained satisfactory dissolubility. Moreover, it was possible to obtain the rapidly disintegrating tablets with very satisfactory properties, i.e., a tablet hardness of 30 N or higher and a disintegration time of 30 s or less, by the addition of croscarmellose as a disintegrant at 2% to the surface-modified solid dispersion and selection of the tableting pressure at 4.5 kN.     

Structure of the electrical double layer on the aqueous solution side of the polarized interface between water and a room-temperature ionic liquid, tetrahexylammonium bis(trifluoromethylsulfonyl)imide

The structure of the electrical double layer on the aqueous solution side has been studied by measuring electrocapillary curves at the polarized interface between a room-temperature ionic liquid (RTIL), tetrahexylammonium bis(trifluoromethylsulfonyl)imide, and water (W) at different concentrations of LiCl. Thermodynamic analysis of the electrocapillary curves indicates that Li+ ions negatively adsorb at the point of zero charge. The adsorption of Li+ and Cl- ions in the polarized potential window of about 200 mV can be explained by the Gouy's double layer model, and the specific adsorption of Li+ and Cl- ions at the RTIL|W interface is negligible within the polarized potential window.     

Relativistic effects and the halogen dependencies in the 13C chemical shifts of CH4−nIn,CH4−nBrn,CCl4−nIn,and CBr4−nIn (n=0–4)

Linear and nonlinear halogen dependencies of the ¹³C magnetic shielding constants of CH_4−nI_n, CH_4−nBr_n, CCl_4−nI_n, and CBr_4−nI_n were fairly reproduced by the ab initio generalized unrestricted Hartree–Fock (GUHF)/finite perturbation (FP) method including spin‐orbit (SO) interaction and spin‐free relativistic (SFR) terms. As seen from the experimental trends, the calculated ¹³C chemical shifts in CCl_4−nI_n and CBr_4−nI_n depend linearly on n=0–4, while those in CH_4−nI_n and CH_4−nBr_n depend nonlinearly. We found that both the linear and nonlinear dependencies are due to the relativistic effects, and especially due to the Fermi–Contact (FC) term originating from the SO interaction. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 528–536, 2001     

p-Nitrophenol permeability and temperature characteristics of an acryloyl-L-proline methyl ester-based porous gel membrane

Thermoresponsive porous gel membranes were synthesized by a simultaneously occurring process consisting of radiation-induced polymerization and crosslinking in aqueous solutions at various concentrations of acryloyl-L -proline methyl ester(A-ProOMe) without a crosslinker. Permeation of p-nitrophenol (PNP) through a thermoresponsive porous gel membrane obtained at a monomer concentration of 80% (w/w) drastically reduced around 14°C, the lower critical solution temperature (LCST) of linear poly(A-ProOMe) in water, from 0.60 × 10⁻³ cm/min at 10°C to no permeation at 18°C, accompanied by changes in both size and shape of pores associated with gel shrinkage. Moreover, it was found that porous gel membranes with a porosity of approximately 60% had a greater PNP permeability constant through porous gel membranes with mutually connected pores obtained at a monomer concentration of 50% (w/w) than individually supported pores obtained at a monomer concentration of 70% (w/w). © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1495–1500, 1998