摘要：In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines(NP-DATAs),synthesis of a series of novel biphenyl-substituted diaryltriazines(BP-DATAs)with a flexible side chain attached at the C-6 position is *** compounds exhibited excellent potency against wild-type(WT)HIV-1 with EC50 values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant *** 5 j and 6 k had the best activity against WT,single and double HIV-1 mutants and reverse transcriptase(RT)enzyme comparable to two reference drugs(EFV and ETR)and our lead compound NP-DATA(1).molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket(NNIBP)attributing to the improved *** preliminary structure-activity relationship and PK profiles were also discussed.

摘要：Taxol is a 'blockbuster' antitumor drug produced by Taxus species with extremely low amount, while its analogue 7-β-xylosyl-10-deacetyltaxol is generally much higher in the plants. Both the fungal enzymes LXYL-P1à1 and LXYL-P1à2 can convert 7-β-xylosyl-10-deacetyltaxol into10-deacetyltaxol for Taxol semi-synthesis. Of them, LXYL-P1à2 is twice more active than LXYLP1à1, but there are only 11 significantly different amino acids in terms of the polarity and acidic-basic properties between them. In this study, single and multiple site-directed mutations at the 11 sites from LXYL-P1à1 to LXYL-P1à2 were performed to define the amino acids with upward bias in activities and to acquire variants with improved catalytic properties. Among all the 17 mutants, E12(A72 T/V91 S) was the most active and even displayed 2.8-and 3-fold higher than LXYL-P1à2 on β-xylosidase andβ-glucosidase activities. The possible mechanism for such improvement was proposed by homology modeling and molecular docking between E12 and 7-β-xylosyl-10-deacetyltaxol. The recombinant yeast GS115-P1 E12-7 was constructed by introducing variant E12, the molecular chaperone gene pdi and the bacterial hemoglobin gene vhb. This engineered yeast rendered 4 times higher biomass enzyme activity than GS115-3.5 K-P1à2 that had been used for demo-scale fermentation. Thus, GS115-P1 E12-7 becomes a promising candidate to replace GS115-3.5 K-P1à2 for industrial purpose.

摘要：A new star-shaped molecule StOF-Br_3 containing oligofluorenes and halogen atoms(Bromine) has been synthesized and studied by Scanning Tunneling Microscopy(STM) at the highly oriented pyrolytic graphite(HOPG) *** have obtained the high-resolution self-assembled STM images,from which the highly ordered and closely packed non-porous arrangements of the StOF-Br_3 molecular selfassemblies at the heptanoic acid/HOPG surface could be *** molecular models and selfassembled StOF-Br_3 architectures have been given in the following ***,we have also figured out the surface free energy by the density functional theory(DFT) calculation,which proved that the halogen...halogen interaction was strong enough to stabilize the ordered molecular *** work verifies the existence of bromine...bromine interactions,and meanwhile provides a kind of effective approach for quickly building ordered molecular nanoarchitectures with large areas and different geometries.

摘要：General anesthetics constitute some of the most important and widely-used therapeutic drugs in the pharmacotherapeutic armamentarium. They are routinely used effectively and with adequate precaution-safety throughout the world for a multitude of clinical applications, predominantly as adjunctive agents for surgical procedures. Nevertheless, they have potential adverse effects (such as a drop in blood pressure and the inhibition of steroid production), particularly in vulnerable populations such as the very young and the frail elderly. It would be desirable therefore to have alternative agents that are just as efficacious, but have a better safety profile in a broader spectrum of patients. Toward this end, an anesthetic based on a unique chemical core (viz., an N-arylpyrrole derivative) has been reported in preclinical models to produce anesthetic effects without hemodynamic suppression. This lead could pave the way for new general anesthetics that are safer and easier to use.

摘要：InAs/GaSb type-II superlattce (T2SL) photodetector structures at the MWIR regime were grown by molecular beam epitaxy. The growth temperature and group-V soaking times were optimized with respect to interface and transport quality. Novel strain compensation schemes with insertion of InSb layers were proposed and tested to be efficient to tune the overall strain between tensile and compressive without degradation of interface and optical quality. The effect of the proposed methods is modeled by analytic functions.? Band structure calculations were also carried out for the proposed T2SL structures to assist optimizing sample designs. Single pixel photodiodes with a low dark current were demonstrated.

摘要：Strategies for CADD vary depending on the extent of structural and other information available regarding the target (enzyme/receptor) and the ligands. Computer-aided drug design (CADD) is an exciting and diverse discipline where various aspects of applied and basic research merge and stimulate each other. In the early stage of a drug discovery process, researchers may be faced with little or no structure activity relationship (SAR) information. The process by which a new drug is brought to market stage is referred to by a number of names most commonly as the development chain or “pipeline” and consists of a number of distinct stages. To design a rational drug, we must firstly find out which proteins can be the drug targets in pathogenesis. In present review we reported a brief history of CADD, DNA as target, receptor theory, structure optimization, structure-based drug design, virtual high-throughput screening (vHTS), graph machines.

摘要：A widely used herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was imprinted on poly (4-vinylpyridine) (4-VP) using (40%) ethyleneglycol dimethacrylate (EGDMA) as crosslinking agent. The classical imprinting technology makes use of a high degree of crosslinking which does not allow the template molecules to move freely. So the binding sites, located in the central area of the three dimensional polymer matrix are hard to be accessed and the template molecules cannot be extracted totally. But here we propose a low crosslinked system with high specificity and selectivity. The imprinted and non-imprinted polymers were characterized by various spectroscopic techniques. The extent of binding was followed by batch equilibration method and compared with the respective non-imprinted polymer. Conditions for maximum specific rebinding were set by altering certain factors like template/monomer ratio, concentration of template solution, rebinding medium, mass of polymer and time of incubation. The selectivity of the imprinted polymer was investigated by comparing the binding with structural analogues of 2,4-D like, phenoxyacetic acid (POA), 4-chlorophenoxyacetic acid (4-CPOA) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). The imprinted polymer exhibited high affinity towards the template molecule and was selectively rebound to the specific sites. The binding towards the structural analogues depends on the number of chlorine in the benzene ring.

摘要：实时荧光PCR技术自问世以来,以其高特异性,高灵敏性,可定量,无污染,而得到了广泛的应用.该技术是根据荧光共振能量转移(fluorescence resonance energy transfer,FRET)原理,设计相应的荧光标记核酸探针,通过PCR反应对相应靶DNA进行均相定性定量测定的技术.根据检测中所使用的荧光探针分类, 目前已经开发出TaqMan,molecular Beacon, Scorpion,LightCycler,Single—labeled probe, ResonSense,Angler以及双链探针等相关技术.本文对该技术的研究进展作一综述.