MD Simulation of AEDG Peptide Complexes with New K2R Dendrimer and Dendrigraft

Biocompatible peptide dendrimers and dendrigrafts have useful properties for application in biomedicine. In previous papers the computational approach for study lysine dendrimers and dendrigrafts as well as their complexes with various medical peptides was used. In this paper the comparison of complex formation between molecules of therapeutic AEDG tetrapeptide and novel K2R peptide dendrimer or DG2 dendrigraft of near the same size and charge was fulfilled. The systems consisting of 16 therapeutic AEDG tetrapeptide molecules and one dendrimer or one dendrigraft were studied by molecular dynamics simulation. Full atomic models of these molecules in water with explicit counterions were used for this goal. First of all, the process of complex formation was studied. It was obtained that peptide molecules were attracted by both branched molecules and were quickly adsorbed by them. Times of complexes formation as well as size, anisotropy and structure of each complex were calculated. It was demonstrated that both K2R dendrimer and DG2 dendrigraft are effective for complexation of these peptide molecules but new dendrimer complex is more stable than dendrigraft complex because it has almost twice more hydrogen bonds with peptide molecules and 33% more ion pairs with their charged groups.

Controllable spontaneous resolution in ultrasmall Cu-Ag bimetallic cluster ion pairs from achiral components

Bimetallic cluster ion pairs containing a quaternary phosphonium and an ultrasmall Cu2Ag3 anionic cluster protected by thiolates: (PPh3R″)[Cu2Ag3(SR′)6] (R′SH = cyclohexylthiol (CySH), R″ = Ph, 1; Me, 2; Et, 3;...

Dendrite-free alkali-metal electrodeposition from contact-ion-pair state induced by mixing alkaline earth cation

Alkali metals, such as lithium and sodium, have been expected to be used for rechargeable metal-anode batteries owing to their low electrode potentials and large capacities. However, the well-known fatal problem, “dendritic growth” causing a dangerous short circuit, is faced while charging the batteries. Here, through a comprehensive study with electrochemical experiments, Raman and soft X-ray emission spectroscopies, density-functional-theory calculation, and molecular dynamic simulations, we provide an advanced guideline for electrolyte design in which a mixture of alkaline earth (Mg, Ca, Ba) salts is used to inhibit dendrite growth of alkali metals (Li, Na) during electrodeposition. Especially, focusing on CaTFSA2, as a salient exemplary alkaline-earth-cation additive, we demonstrate that dendrite-free morphology upon alkali-metal electrodeposition can successfully be attained by modifying their solvation structures in the dual-cation electrolyte systems. Adding divalent Ca2+ promotes alkali cation (Li+ or Na+) to form the contact ion pairs (CIPs) with the counter anions, which replaces the solvent-separated ion pairs (SSIPs) commonly existing in single-cation electrolytes. Such CIPs related to alkali cations would separate Ca2+ ions distantly to shield the strong coulomb interaction among the divalent cations. The stronger binding of the CIPs would retard the desolvation kinetics of alkali cations and, consequently, realizes a severely constrained alkali-metal electrodeposition in a reaction-limited process that is required for the dendrite-free morphology. This work provides prospects to construct dual-cation electrolytes for dendrite-free alkali-metal-anode batteries utilizing the concerted interactions between monovalent and multivalent cations.

Primary Ionization Density Produced by Charged Fragments in the Working Volume of the Fission Chambers

The question of the spatial distribution of ion pairs created by 235U fission fragments in the active volume of the fission chamber has been studied. The formulas of the spatial distribution of ion pairs in cylindrical fission chambers are proposed, which allows you to evaluate correctly the density of ion pairs in any point in the sensitive volume of the fission chamber

Young and Old Leaves Physiological and Metabolite Profiles Analysis on Amino Acids and Organic Acids in Wild Soybean Seedlings Under Nitrogen Deficiency

Background As an important germplasm resource, wild soybean has good tolerance to complex stress environment stress. This study described the differences of physiological and metabolomic changes between common wild soybean (GS1) and the barren tolerance wild soybean (GS2) under low nitrogen (LN) stress. Results The result showed the barren tolerance wild soybean young leaves can maintain relatively stable chlorophyll content and increased the contents of Car;Photosynthetic rate and transpiration rate decreased significantly in in the barren tolerance wild soybean old leaves, but there was no significant change in young leaves; the barren tolerance wild soybean enhanced the enrichment of beneficial ion pairs such as zinc, calcium and phosphorus. The metabolism of amino acids and organic acids in the barren tolerance wild soybean old leaves was vigorous, a large number of beneficial amino acids such as GABA, asparagine and proline were enriched, and the metabolites related to TCA cycle were significantly increased. Conclusion the barren tolerance wild soybean can ensure the nitrogen supply of young leaves by inhibiting the photosynthetic response of old leaves; the relatively stable growth of young leaves also benefits from the effective transport and reuse of beneficial ions from old leaves; More importantly, the enhanced metabolism of specific amino acids and organic acids in GS2 old leaves seemed to play an important role in resisting LN stress. GABA and Asparagine played substantial roles in N storage, C/N balance, antioxidant defense and act as signaling molecule to help GS2 to resist LN stress. Difference organic acids in the old leaves of GS2 increased which could improve the utilization rate of N in the soil. In addition, the strength of fatty acids catabolism and TCA cycle in GS2 old leaves provided energy base for substance transport. The analysis of physiological and metabolite may provide a new perspective for revealing the importance of substance transport and reuse in different plant parts to resist abiotic stress.

Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier

Imaging-guided delivery is developed for hydrophobic drugs, and to a much lesser extent, hydrophilic ones. In this work we have designed a novel strategy for real-time monitoring of hydrophilic drug delivery. Traditionally, the drug and the dye are covalently attached to a nanocarrier or are electrostatically adsorbed. Recently, we found an efficient way to bind the drug by ion-paring with an appropriate counter-ion to form the aggregate that embeds a hydrophobic dye with a considerable fluorescence enhancement. We synthesized a series of carbocyanine dyes of hydrophobicity sufficient for solubilization in hydrophobic ion pairs, which restores their emission in the near-infrared (NIR) region upon the formation of the ternary aggregates. To avoid using toxic surfactants, we applied an amphiphilic polymer-oligomer poly(hexamethylene guanidine) (PHMG) as a counter-ion. Сeftriaxone was used as a model hydrophilic drug ensuring the highest fluorescent signal. The so-formed drug–counter-ion–dye aggregates were encapsulated into a cross-linked maleated chitosan carrier. Confocal laser scanning microscopy (CLSM) studies have demonstrated internalization of the encapsulated model drug by breast adenocarcinoma cells at 40 min after treatment. These results suggest the potential application of hydrophobic ion pairs containing an NIR dye in imaging-guided delivery of hydrophilic compounds.

Quantum Surprises from the Watson-Crick and Hoogsteen G·C Nucleobase Pairs: A Comprehensive QM/QTAIM Investigation

In this study at the MP2/6-311++G(d,p)//B3LYP/6-311++G(d,p) level of theory in the isolated state it was revealed 14 novel physico-chemical mechanisms of the tautomerization of the G·C nucleotide base pairs in the Watson-Crick G·C(WC) / G*·C*(WC), reverse Watson-Crick G*·C*(rWC) / G·C*O2(rWC), Hoogsteen G*t·C*(H) / G*N7·C(H) or reverse Hoogsteen G*t·C*(rH) / G*tN7·C(rH) configurations into the wobble (wWC, wH) and reverse wobble (rwWC, rwН) base pairs: 1. G·C(WC)↔G·C*(rwWC), 2./3. G*·C*(WC)↔G·C*(rwWC)/G*N2·C*(rwWC), 4. G*·C*(rWC)↔G*·C(wWC), 5. G·C*O2(rWC)↔G·C*(wWC); 6./7./8./9. G*t·C*(H)↔G*t·C(rwН)/G*t·C*O2(wH)/G*t·C*O2(rwН)/G*tN7·C*(rwН)↔G*t·C*O2(rwН), 10. G*N7·C(H)↔G*t·C(wH) amino, 11./12. G*t·C*(rH)↔G*N7·C*(wН)/G*t·C(wН), 13. G*tN7·C(rH)↔G*tN7·C*(wН)↔G*t·C(wН) and 14. G*N7·C*(rwH)↔G*N7·C*(rwH) perp↔G-·C+(wH)↔G*t·C(rwН) reaction pathways. It was established that the presence in the base pair of the two anti-parallel neighboring H-bonds is a necessary and sufficient condition for the implementation of such transformations, since it enables intermolecular proton transfer between the bases inside the base pair. It was found out that these tautomeric transitions are controlled by the TSs with quasi-orthogonal structure, which are tight G+·C-/G-·C+ ion pairs, joined by at least two parallel intermolecular H-bonds, connected on a common negatively charged endocyclic N-/C- atoms – proton acceptor. All reaction pathways have been reliably confirmed. These transitions are accompanied by the changing of the mutual cis-orientation of the N9H and N1H glycosidic bonds of the bases on the trans-orientation and vice versa. These data complement the reported earlier mechanisms of the tautomerisations of the classical A·T and G·C DNA base pairs. Experimental verification of the novel G·C nucleobase pairs is looking as an attractive task for the future research.

Maturation process and characterization of a novel thermostable and halotolerant subtilisin-like protease with high collagenolytic but low gelatinolytic activity

Enzymatic degradation of collagen is of great industrial and environmental significance; however, little is known about thermophile-derived collagenolytic proteases. Here, we report a novel collagenolytic protease (TSS) from thermophilic Brevibacillus sp. WF146. The TSS precursor comprises a signal peptide, an N-terminal propeptide, a subtilisin-like catalytic domain, a β-jelly roll (βJR) domain, and a prepeptidase C-terminal (PPC) domain. The maturation of TSS involves a stepwise autoprocessing of the N-terminal propeptide and the PPC domain, and the βJR rather than the PPC domain is necessary for correct folding of the enzyme. Purified mature TSS displayed optimal activity at 70°C and pH 9.0, a half-life of 1.5 h at 75°C, and an increased thermostability with rising salinity up to 4 M. TSS possesses an increased number of surface acidic residues and ion pairs, as well as four Ca 2+ -binding sites, which contribute to its high thermostability and halotolerance. At high temperatures, TSS exhibited high activity toward insoluble type I collagen and azocoll, but showed a low gelatinolytic activity, with a strong preference for Arg and Gly at the P1 and P1’ positions, respectively. Both the βJR and PPC domains could bind but not swell collagen, and thus facilitate TSS-mediated collagenolysis via improving the accessibility of the enzyme to the substrate. Additionally, TSS has the ability to efficiently degrade fish scale collagen at high temperatures. IMPORTANCE Proteolytic degradation of collagen at high temperatures has the advantages of increasing degradation efficiency and minimizing the risk of microbial contamination. Reports on thermostable collagenolytic proteases are limited, and their maturation and catalytic mechanisms remain to be elucidated. Our results demonstrate that the thermophile-derived TSS matures in an autocatalytic manner, and represents one of the most thermostable collagenolytic proteases reported so far. At elevated temperatures, TSS prefers hydrolyzing insoluble heat-denatured collagen rather than gelatin, providing new insight into the mechanism of collagen degradation by thermostable collagenolytic proteases. Moreover, TSS has the potential to be used in recycling collagen-rich wastes such as fish scales.

Creation of stable water-free antibody based protein liquids

Antibodies represent highly specific and high binding affinity biomolecular recognition elements for diagnostic assays, biosensors, and therapeutics, but are sensitive to denaturation and degradation. Consequently, the combination of existing in a hydrated state with a large and complex biomolecular structure results in loss of antibody-antigen binding, limited shelf-life, and decreased sensor response over time and under non-optimal conditions. The development and use of water-free protein liquids has led to stabilization of labile biomolecules, solvents for biotransformation reactions, and formation of new bio-composites with incompatible materials. Here, we exploit the polycationic nature of modified antibodies and their ability to form ion pairs for the conversion of primary Immunoglobulin G antibodies into stable protein liquids that retained more than 60% binding activity after repeated heating up to 125 °C, and demonstrate compatibility with thermoplastics.