Drug discovery based on the structure of FKBP12: Design, synthesis and evaluation of L-1,4-thiazane-3-carboxylic acid derivatives as neuroimmunophilin ligands

By choosing neuroimmunophilin FKBP12 as a therapeutical target, we have attempted to discover a new structural drug for treating neurodegenerative disease. This drug should possess neurotrophic activity and not affect the immune system. Based on the crystal structure of FKBP12, FK506 and Calcineurin complex, a series of small organic molecules were designed. These molecules were to have the ability of binding to FKBP12 in a virtual screening. By using a solution parallel synthetic method, these compounds were synthesized. The neuroprotective and neuroregenerative activities of these compounds were evaluated by binding assays, PC12 cells survival and neurite outgrowth model, chick dorsal root ganglion cultures (DRG) and 6-OHDA lesioned mice sympathetic nerve endings model. The evaluation results of these compounds showed that compound N308 has great promise as a candidate for a neuroprotective and neuroregenerative agent.     

Self-diffusion measurements in In_2O_3 isotopic heterostructures:Oxygen vacancy energetics

正As a prototypical transparent conducting oxide (TCO), In2O3after heavily doped with Sn exhibits a priority in optoelectronic applications involving organic light emitting diodes(OLED) and organic photovoltaics (OPVs)[1,2]. Mean-     

BBOT诱导环糊精形成纳米管及二次组装体

本文报道了有机分子BBOT(2,5-bis(5′-tert-butyl-2-benzoxazoyl)thiophene)与α-、β-、γ-环糊精(cyclodextrins,CDs)的相互作用.BBOT可以与这3种环糊精进行不同方式的组装:BBOT与α-CD形成1:2(客体:主体)包合物;当BBOT浓度较低时与β-CD形成1:1包合物,浓度较高时则与β-CD形成纳米管及二次组装体;对于γ-CD而言,在我们所研究的BBOT浓度范围内都可与其形成纳米管及二次组装体.研究发现,BBOT-β-CD纳米管和BBOT-γ-CD纳米管的结构存在一定差异.     

Ga<Subscript>Zn</Subscript>-V<Subscript>Zn</Subscript> acceptor complex defect in Ga-doped ZnO

Gallium (Ga)-doped ZnO is regarded as a promising plasmonic material with a wide range of applications in plasmonics. In this study, zinc self-diffusion experiments are adopted to disclose the nature of the dominant compensating defect in Ga-doped ZnO isotopic heterostructures. The (Ga_Zn-V_Zn)^? complex defect, instead of the isolated V_Zn^2?, is identified as the predominant compensating acceptor center responsible for the low donor doping efficiency. The comparative diffusion experiments operated by the secondary ion mass spectrometry reveal a ~0.78 eV binding energy of this complex defect, which well matches the electrical activation energy derived from the temperature-dependent Hall effect measurements (~(0.82±0.02) eV). These findings contribute to an essential understanding of the (Ga_Zn-V_Zn)^? complex defect and the potential engineering routes of heavily Ga-doped ZnO.     

Synthesis,crystal structure,thermal behavior and luminescence property of a cobalt(II) complex of pyridine-2,6-dicarboxylic acid containing benzimidazole as auxiliary ligand

The new cobalt(II) complex [Co(pydca)(bim)₃] (1) (where H₂pydca = pyridine-2,6-dicarboxylic, bim = benzimidazole) has been synthesized and characterized by elemental analysis, Infrared spectroscopy, X-ray single crystal analysis, thermogravimetric and fluorescent analysis. Single crystal X-ray diffraction analysis reveals that the mononuclear complexes are linked by N–H…O hydrogen bonds. Fluorescent analysis reveals that complex 1 exhibits intense luminescence in ethanol solution at room temperature.     

Drug discovery based on the structure of FKBP12: Design,synthesis and evaluation of <Emphasis Type="Italic">L</Emphasis>-1,4-thiazane-3-carboxylic acid derivatives as neuroimmunophilin ligands

By choosing neuroimmunophilin FKBP12 as a therapeutical target, we have attempted to discover a new structural drug for treating neurodegenerative disease. This drug should possess neurotrophic activity and not affect the immune system. Based on the crystal structure of FKBP12, FK506 and Calcineurin complex, a series of small organic molecules were designed. These molecules were to have the ability of binding to FKBP12 in a virtual screening. By using a solution parallel synthetic method, these compounds were synthesized. The neuroprotective and neuroregenerative activities of these compounds were evaluated by binding assays, PC12 cells survival and neurite outgrowth model, chick dorsal root ganglion cultures (DRG) and 6-OHDA lesioned mice sympathetic nerve endings model. The evaluation results of these compounds showed that compound N308 has great promise as a candidate for a neuroprotective and neuroregenerative agent. Supported by the National Basic Research Program of China (Grant No. G1998051107) and Hi-tech Research and Development Program of China (Grant No. 2002AA233051)     

Robustness and breakup of the spiral wave in a two-dimensional lattice network of neurons

The robustness and breakup of spiral wave in a two-dimensional lattice networks of neurons are investigated. The effect of small- world type connection is often simplified with local regular connection and the long-range connection with certain probability. The network effect on the development of spiral wave can be better described by local regular connection and changeable long-range connection probability than fixed long-range connection probability because the long-range probability could be changeable ...     

A relative local variational principle for topological pressure

We define the relative local topological pressure for any given factor map and open cover,and prove the relative local variational principle of this pressure.More precisely,for a given factor map π:(X,T)→(Y,S) between two topological dynamical systems,an open cover U of X,a continuous,real-valued function f on X and an S-invariant measure ν on Y,we show that the corresponding relative local pressure P(T,f,U,y) satisfies sup μ∈M(X,T){ hμ(T,U|Y)+∫X f(x)dμ(x) :πμ=ν}=∫Y P(T,f,U,y)dν(y),where M(X,T) denotes the family of all T-invariant measures on X.Moreover,the supremum can be attained by a T-invariant measure.     

Formation of nanotubes and secondary assemblies of cyclodextrins induced by BBOT

The study of cyclodextrin nanotubes is a significant topic among the self-assembly behaviors of cyclodextrins. We report herein the interaction of 2,5-bis(5′-tert-butyl-2-benzoxazoyl)thiophene (BBOT) with α-, β-, γ-cyclodextrins (CDs). It has been discovered that the reaction patterns of BBOT with CDs are remarkably different. β-CD forms a simple inclusion complex with BBOT in a stoichiometry of 1:2 (guest:host). β-CD forms a 1:1 inclusion complex with BBOT at its low concentration. At higher concentration of BBOT, the nanotube and secondary assembly of β-CD are formed. As for γ-CD, the nanotube and secondary assembly are formed within the whole concentration range of BBOT studied. The structure of γ-CD nanotubes is different from that of β-CD nanotubes to a certain extent.