Novel Dual‐Site‐Binding Neuraminidase Inhibitor from Virtual Screening by Pharmacophore and Molecular Dynamics Methods

Neuraminidase is a significant anti‐influenza target that plays crucial role in virus replication cycle. The discovery of 150‐cavity in Group‐1 neuraminidase provides us a novel mentality of designing inhibitor which can bind with both conserved site and 150‐cavity. In order to discover novel dual‐site‐binding inhibitors, a 3D chemical‐feature‐based pharmacophore model was established to cover dual‐site in neuraminidase. The dual‐site‐binding model was consistent in predicting the binding conformation of Group‐1 neuraminidase inhibitor and applied for virtual screening of Specs database. Compound 4 (ZINC05790048) that aligned well to the model was selected after multiple filtrations for molecular dynamics simulations, indicating improved binding energy with neuraminidase. It can sever as the lead compound for a novel series of inhibitors.     

γ-Ray-Radiation-Scissioned Chitosan as a Gene Carrier and Its Improved in uitro Gene Transfection Performance

Chitosan (CS) is expected to be an ideal gene carrier for its high biosafety. In this work, CS with low molecular weight were prepared through the γ-ray radiation on the acetic acid solution of CS. The CS chains were scissioned under the γ-ray radiation, and the molecular weight (MW) of CS decreased with the absorbed dose. When the absorbed dose was above 30 kGy, the molecular weight of CS decreased about an order of magnitude. The γ-ray-radiation-scissioned CS can e ectively bind with plasmid (pEGFP) through complex coacervation method, forming pEGFP/ γ-ray-radiation-scissioned CS complex particles with a size of 200-300 nm. The complex particles have good stability and little cytotoxicity. The in uitro gene transfection efficiencies of the pEGFP/ γ-ray-radiation-scissioned CS complex particles were investigated by fluorescence microscope and flow cytometry. The results showed that the gene vectors using γ-ray-radiation-scissioned CS as the carrier will possess better gene transfection efficiency than those using natural high-MW CS as the carrier. The higher the absorbed dose, the smaller the MW of CS and the better transfection efficiency of the corresponding gene vector. This work provides a green and simple method on the preparation of CS-based gene vectors with high efficiency and biosafety.     

Encapsulation of nanocrystals with responsive gels for spatial optical identification

A tripeptide (β-AspFF) gelator was designed and synthesised using solid-phase peptide synthesis. The as-prepared gelator formed a stable and clear multi-responsive gel in toluene solution. Encapsulating the quantum dots with β-AspFF effectively increased stability and antioxidisation ability which are beneficial for optical identification.     

Predicting the Standard Enthalpy (ΔHo f) and Entropy (So) of Alkanes by Artificial Neural Networks

Abstract

Artificial Neural Networks (ANNs) with Extended Delta-Bar-Delta (EDBD) back propagation learning algorithm have been developed to predict the standard enthalpy and entropy of 87 acyclic alkanes. Molecular weight, boiling point and density of the compounds were used as input parameters. The network's architecture and parameters were optimized to give maximum performances. The best network was a 3-6-2 ANN, and the optimum learning epoch was about 1320. The results show that the maximum relative errors of enthalpy and entropy are less than 3%. They reveal that the performances of ANNs for predicting the enthalpy and entropy of alkanes are satisfying.     

Destabilization of artificial biomembrane induced by the penetration of tryptophan

The effect of tryptophan on the membrane stability was studied by using three artificial biological membranes including liposome, Langmuir monolayer and solid supported bilayer lipid membrane (s-BLM) as models. All the results indicate that the penetration of tryptophan can destabilize different artificial biological membranes. The diameter of liposome and the leakage of calcein from liposome increased with the increase of tryptophan concentration because the penetration of tryptophan was beneficial for dehydrating the polar head groups of lipids and the formation of fusion intermediates. π-A isotherms of lecithin on the subphase of tryptophan solution further confirm that tryptophan can penetrate into lipid monolayer and reduce the stability of lipid monolayer. When the concentration of tryptophan increased from 0 to 2 × 10⁻³ mol L⁻¹, the limiting molecular area of lecithin increased from 110.5 to 138.5 Å², but the collapse pressure of the monolayer decreased from 47.6 to 42.3 mN m⁻¹, indicating the destabilization of lipid monolayer caused by the penetration of tryptophan. The resistance spectra of s-BLM demonstrate that the existence of tryptophan leads to the formation of some defects in s-BLM and the destabilization of s-BLM. The values of electron-transfer resistance and double layer capacitance respectively decreased from 5.765 × 10⁶ Ω and 3.573 × 10⁻⁸ F to 1.391 × 10⁶ Ω and 3.340 × 10⁻⁸ F when the concentration of tryptophan increased from 0 to 2 × 10⁻³ mol L⁻¹. Correspondingly, the breakdown voltage of s-BLM decreased from 2.51 to 1.72 V.