The heteroepitaxial growth of KDP/ADP

Crystal growth rules of mixture crystals KADP (potassium dihydrogen phosphate (KDP) and ammonium dihydrogen phosphate (ADP)) have been analyzed based on the solubility product principle. The heteroepitaxial layers have been obtained by immersing KDP (ADP) substrate into the ADP (KDP) saturated solution at 313 K. The micromorphology indicates that small growing points on different planes show the self‐similar property compared to the bulk crystal's morphology. The process of epitaxial growth depends on not only form the lattice match but also form crystallizing kinetics which is the main influencing factor. Moreover, it can infer from the micromorphology on the surface of the mixed crystal that the dissolving of substrates will form mixed solution on epitaxial surface. What's more, corrosion phenomenon gets more and more evident with increasing times of epitaxial growth and it will be harder to form transparent epitaxial layers due to the increasing tension of epitaxial layers. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

β-Biguanidinium-cyclodextrin: a supramolecular mimic of mitochondrial ADP/ATP carrier protein

We reported a novel mono-β-cyclodextrin derivative, mono-6-deoxy-6-biguanidino-β-cyclodextrin (β-biGCD), which was investigated as a mimic of ADP/ATP carrier (AAC). Its affinity toward AMP, ADP, and ATP was evaluated by means of isothermal titration calorimetry (ITC). The association constants (K_a) of β-biGCD binding to AMP, ADP, and ATP were determined to be (1.07±0.04)×10⁶, (5.86±0.02)×10⁶, and (4.33±0.06)×10⁶ L mol⁻¹, respectively, which were 100-fold higher than mono-guanidino-β-cyclodextrin (ca. 10⁴ L mol⁻¹). UV spectroscopic titrations further confirmed the above results. The interaction between β-biGCD and nucleotides was probed by docking simulation. These results reveal that the biguanidinium moiety mimics the arginine residues of mitochondrial AAC protein.     

An anthracene-modified β-cyclodextrin that distinguishes adenosine phosphates fluorescently

A β-cyclodextrin derivative (AnCD) with the diamino anthracene was presented and studied, which can distinguish AMP from ADP and ATP via fluorescence titration.     

Proteomic characterization of human platelet-derived microparticles

Microparticles (MPs) are small fragments of apoptotic or activated cells that may contribute to pathological processes in many diseases. Platelet-derived MPs (PMPs) are the most abundant type of MPs in human blood. To characterize the proteins in PMPs we used a shotgun proteomics approach by nanoHPLC separation followed by MS analysis on an LTQ Orbitrap XL. PMPs were produced from isolated platelets stimulated with adenosine diphosphate (ADP). We developed an analytical platform constituted by two different steps: in the first one we used a standard shotgun strategy; in the second one, to improve low-molecular weight, low-abundance-proteins identification, the samples were fractionated using hydrogel nanoparticles, an enrichment system based on a mixed mechanism of dimensional exclusion and colorant affinity. This was chosen to tackle a common issue with shotgun approaches, in which the low-abundance proteins are not detected when surveys are on a broad scale. By means of the entire analytical platform, we identified 603 proteins, 243 of which were not previously identified. A simple and straightforward procedure for the study of PMPs was provided, producing a tool for further understanding their biological and pathological roles, and a baseline for future studies aimed at discovering biomarkers involved in several diseases.     

The first examples of ilexgenin A hybrids as a new class of multi-potent, anti-platelet agents

Seventeen novel ilexgenin A hybrids（lA-aspirin） and（IA-NO）,as donor hybrids（IA-NO will release NO in vivo and function as NO donor）,were designed and synthesized in order to develop new multi-targeting agents for the treatment of platelet disorders.Their in vitro activities against ADP,AA and thrombin were evaluated.As a result,IA hybrids achieved substantial increases in the three tested pathways compared with IA.Encouragingly,the most potent hybrid compounds 6d and 14d displayed about 8-fold higher potency than aspirin,and 3-fold higher potency than the simultaneous administration of aspirin and IA in inhibiting ADP-induced aggregation with IC₅₀ values of 0.15 mmol/L and 0.14 mmol/L,respectively. The results suggest these IA hybrids are good candidates for multi-target therapies,and especially,may be considered as promising ADP agonists.     

动态规划求解空间双臂机器人非完整运动最优控制问题

通过自适应动态规划研究自由漂浮空间双臂机器人运动的最优控制问题．针对空间双臂机器人的非完整性运动,采用自适应动态规划(Adaptive Dynamic Programming, ADP)方法求解其最优控制问题．根据多体动力学理论,推导了载体位置、姿态均无控制条件下,双臂空间机器人满足的系统动量守恒关系的非完整约束方程,并将其转化为控制系统的状态方程,从而将双臂空间机器人的非完整运动规划问题转化为对非线性系统的控制问题．文中根据自适应动态规划网络结构,利用神经网络来近似性能指标函数,进而用龙格库塔法求解状态变量．并给出了适合该类问题的一种效用函数具体表达式,保证了空间双臂机器人到达期望位置后不再继续运动．实现了对空间双臂机器人非完整运动规划的最优控制．数值仿真实验验证了ADP对求解空间双臂机器人非完整运动规划最优控制问题的有效性．     

Effect of Urea on Metastable Zone Width,Induction Time and Nucleation Parameters of Ammonium Dihydrogen Orthophosphate

Enhancement of the metastable zone width in ammonium dihydrogen ortho phosphate (ADP) was achieved by the addition of the organic compound Urea to ADP solution. The metastable zone width studies were carried out for various temperature cooling rates and the nucleation parameters are studied. The induction period was studied and the critical nucleation parameters calculated based on classical theory for homogeneous nucleation are discussed. The critical nucleation parameters increase with the increase in concentration of doping.     

Coumarin Derivatives Inhibit ADP-Induced Platelet Activation and Aggregation

Coumarin was first discovered in Tonka bean and then widely in other plants. Coumarin has an anticoagulant effect, and its derivative, warfarin, is a vitamin K analogue that inhibits the synthesis of clotting factors and is more widely used in the clinical treatment of endovascular embolism. At present, many artificial chemical synthesis methods can be used to modify the structure of coumarin to develop many effective drugs with low toxicity. In this study, we investigated the effects of six coumarin derivatives on the platelet aggregation induced by adenosine diphosphate (ADP). We found that the six coumarin derivatives inhibited the active form of GPIIb/IIIa on platelets and hence inhibit platelet aggregation. We found that 7-hydroxy-3-phenyl 4H-chromen-4-one (7-hydroxyflavone) had the most severe effect. In addition, we further analyzed the downstream signal transduction of the ADP receptor, including the release of calcium ions and the regulation of cAMP, which were inhibited by the six coumarin derivatives selected in this study. These results suggest that coumarin derivatives inhibit coagulation by inhibiting the synthesis of coagulation factors and they may also inhibit platelet aggregation.     

A selective ATP chromogenic sensor for use in an indicator displacement assay

We synthesized a dinuclear Zn²⁺ complex that is useful as a sensor for ATP in a DMSO/H₂O (1:9, v/v) solvent system via a simple indicator displacement assay (IDA). This chromogenic sensor method can be used to analyze 0.1-2.0 μM of ATP with no interference from ADP or AMP.     

Acid dissociation constants of uridine-5′-diphosphate compounds determined by phosphorus nuclear magnetic resonance spectroscopy and internal pH referencing

The acid dissociation constant (pK_a) of small, biological molecules is an important physical property used for investigating enzyme mechanisms and inhibitor design. For phosphorus-containing molecules, the ³¹P nuclear magnetic resonance (NMR) chemical shift is sensitive to the local chemical environment, particularly to changes in the electronic state of the molecule. Taking advantage of this property, we present a ³¹P NMR approach that uses inorganic phosphate buffer as an internal pH reference to determine the pK_a values of the imide and second diphosphate of uridine-5′-diphosphate compounds, including the first reported values for UDP-GlcNAc and UDP-S-GlcNAc. New methods for using inorganic phosphate buffer as an internal pH reference, involving mathematical correction factors and careful control of the chemical shift reference sample, are illustrated. A comparison of the newly determined imide and diphosphate pK_a values of UDP, UDP-GlcNAc, and UDP-S-GlcNAc with other nucleotide phosphate and thio-analogs reveals the significance of the monosaccharide and sulfur position on the pK_a values.