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71.
Synthesis of New DNA G‐Quadruplex Constructs with Anthraquinone Insertions and Their Anticoagulant Activity 下载免费PDF全文
1,4‐Dihydroxyanthraquinone and 1,8‐dihydroxyanthraquinone were alkylated with 3‐bromopropan‐1‐ol and subsequently transformed into the corresponding DMT protected phosphoramidite building blocks for insertion into loops of the G‐quadruplex of the thrombin binding aptamer (TBA). The 1,4‐disubstituted anthraquinone linker led to a significant stabilization of the G‐quadruplex structure upon replacing a T in each of two neighboring lateral TT loops and a 26.2° increase in thermal melting temperature was found. CD Spectra of the modified quadruplexes confirmed anti‐parallel conformations in all cases under potassium buffer conditions as previously observed for TBA. Although the majority of the anthraquinone modified TBA analogues showed a decrease in clotting times in a fibrinogen clotting assay when compared to TBA, modified aptamers containing a 1,8‐disubstituted anthraquinone linker replacing G8 or T9 in the TGT loop showed improved anticoagulant activities. Molecular modeling studies explained the increased thermal melting temperatures of anthraquinone‐modified G‐quadruplexes. 相似文献
72.
设计了一个简单、通用、基于核酸适配体无标记的高敏感、高专一检测凝血酶的荧光方法。以无标记凝血酶核酸适配体单链DNA为识别元素,Pico Green染料传导互补双链的荧光信号。Pico Green是一种不对称菁,当其单独存在时不产生荧光信号,而当其被吸附到互补的双链DNA上时,可产生很强的荧光信号,但被吸附到单链DNA上时,却无明显的信号改变。基于该性质,将其用于凝血酶的检测。该方法对凝血酶的响应线性范围为1.0×10~(-14)~1.0×10~(-7)mol/L,相关系数(r~2)为0.99,检出限为1.0×10~(-14)mol/L。1.0×10~(-8)mol/L两种干扰物质(牛血清蛋白和细胞色素C)的存在不影响凝血酶的检测,表明该方法对凝血酶具有非常好的专一性。该方法成功应用于对人血清样品的检测,其平均回收率为97%~102%。方法可简单、灵敏、特异性地检测凝血酶,有望用于医学临床诊断等领域。 相似文献
73.
Biao Zeng Guang-Da Liu Bao-Bao Zhang Shan-shan Wang Rui Ma Bei-Shan Zhong 《Natural product research》2016,30(9):1001-1008
A new triterpene saponin, 3β,16β,23α,28β,30β-pentahydroxyl-olean-11,13(18)-dien-3β-yl-[β-d-glucopyranosyl-(1→2)]-[β-d-glucopyranosyl-(1→3)]-β-d-fucopyranoside, was named Clinoposaponin D (1), together with six known triterpene saponins, buddlejasaponin IVb (2), buddlejasaponin IVa (3), buddlejasaponin IV (4), clinopodisides D (5), 11α,16β,23,28-Tetrahydroxyolean-12-en-3β-yl-[β-d-glucopyranosyl-(1→2)]-[β-d-glucopyranosyl-(1→3)]-β-d-fucopyranoside (6) and prosaikogenin A (7), and two known triterpenes, saikogenin A (8) and saikogenin F (9) were isolated from Clinopodium chinense (Benth.) O. Kuntze. Their structures were elucidated on the basis of 1D, 2D NMR and MS analysis. Meanwhile, the effects of all compounds on rabbit platelet aggregation and thrombin time (TT) were investigated in vitro. Compounds 4 and 7 had significant promoting effects on platelet aggregation with EC50 value at 53.4 and 12.2 μM, respectively. In addition, the highest concentration (200 μM) of compounds 2 and 9 shortened TT by 20.6 and 25.1%, respectively. 相似文献
74.
Highly Sensitive Voltammetric Thrombin Aptamer Sensor Based on the Synergistic Effect of Doping/Depositing Gold Nanoparticles in Polydopamine Film 下载免费PDF全文
A highly sensitive square‐wave voltammetric thrombin (TB) aptamer sensor was developed using functional polydopamine (PD) film by doping and depositing gold nanoparticles into the bulk and the surface of PD. The aptamer sensor was fabricated by immobilizing a thiolated TB‐binding aptamer (TBA) on the AuNPs‐doped/deposited PD film. AuNPs‐supported methylene blue labels were used for the detection of human α‐TB. Under the optimized conditions, the aptamer sensor’s dynamic range and the detection limit were determined to be 2.0 pM–50 nM and 0.97±0.06 pM, respectively. Finally, the proposed aptamer sensor was successfully examined in human serum samples and satisfactory results were obtained. 相似文献
75.
《Journal of separation science》2017,40(15):3161-3167
The dynamic binding status between the thrombin and its G‐quadruplex aptamers and the stability of its interaction partners were probed using our previously established fluorescence‐coupled capillary electrophoresis method. A 29‐nucleic acid thrombin binding aptamer was chosen as a model to study its binding affinity with the thrombin ligand. First, the effects of the cations on the formation of G‐quadruplex from unstructured 29‐nucleic acid thrombin binding aptamer were examined. Second, the rapid binding kinetics between the thrombin and 6‐carboxyfluorescein labeled G‐quadruplex aptamer was measured. Third, the stability of G‐quadruplex aptamer–thrombin complex was also examined in the presence of the interfering species. Remarkably, it was found that the complementary strand of 29‐nucleic acid thrombin binding aptamer could compete with G‐quadruplex aptamer and thus disassociated the G‐quadruplex structure into an unstructured aptamer. These data suggest that our in‐house established fluorescence‐coupled capillary electrophoresis assay could be applied to binding studies of the G‐quadruplex aptamers, thrombin, and their ligands, while overcoming the complicated and costly approaches currently available. 相似文献
76.
以Ce3+为中心离子,N,N-二甲基甲酰胺(DMF)为有机配体,通过温度调节,合成系列形貌和电化学信号不同的铈配合物(Ce-COPs)。筛选出电化学信号最强的多面体状Ce-COP为信号探针。通过凝血酶(TB)与TB适体链之间的特异性识别作用,设计了一种简单通用的TB适体传感器。最优实验条件下,该传感器对TB的线性响应范围为1.0 fmol·L-1~1.0 nmol·L-1,检测限为0.94 fmol·L-1。此外,本方案方法与商品人凝血酶(TM) ELISA试剂盒检测结果相近。结果表明,构建的传感器具有良好的灵敏度、特异性、选择性和稳定性。 相似文献
77.
78.
79.
凝血酶时间法测定家兔尿液及胆汁中r-水蛭素 总被引:1,自引:0,他引:1
建立了一种生物测定法---凝血酶时间法(TT法)以测定家兔尿液及胆汁中的r-水蛭素(r-Hirudin,rH),从而为rH的排泄动力学研究提供测定方法学。本方法依据rH的抗凝血酶活性,以logTT延长率对rH浓度构建标准曲线。家兔尿液或胆汁10μL,依次加入40μL空白兔血浆、50μL Tris-HCl缓冲液(pH7.4),以及50μL浓度为5U/mL的凝血酶溶液,由血凝仪记录凝血时间并计算凝血时间延长百分率,从标准曲线求出待测尿液及胆汁中的rH浓度。TT延长百分率(y)经对数转换与尿液或胆汁中rH浓度(x,mg/L)呈线性相关(r>0.99),线性范围0.49~2.50mg/L;检出限为0.49mg/L。高、中、低三种浓度rH尿及胆汁标准溶液日内及日间精密度(RSD)均<10%,方法回收率>95%,稀释回收率>91.9%,室温及-20℃保存至少8h及半月内稳定。应用上述方法测定家兔静脉注射rH后尿及胆汁药物浓度以及研究尿药排泄动力学,均表明本研究建立的TT法精密度和回收率高,结果准确可靠,符合药动学要求。 相似文献
80.
Kamphausen S Höltge N Wirsching F Morys-Wortmann C Riester D Goetz R Thürk M Schwienhorst A 《Journal of computer-aided molecular design》2002,16(8-9):551-567
The design of molecules with desired properties is still a challenge because of the largely unpredictable end results. Computational methods can be used to assist and speed up this process. In particular, genetic algorithms have proved to be powerful tools with a wide range of applications, e.g. in the field of drug development. Here, we propose a new genetic algorithm that has been tailored to meet the demands of de novo drug design, i.e. efficient optimization based on small training sets that are analyzed in only a small number of design cycles. The efficiency of the design algorithm was demonstrated in the context of several different applications. First, RNA molecules were optimized with respect to folding energy. Second, a spinglass was optimized as a model system for the optimization of multiletter alphabet biopolymers such as peptides. Finally, the feasibility of the computer-assisted molecular design approach was demonstrated for the de novo construction of peptidic thrombin inhibitors using an iterative process of 4 design cycles of computer-guided optimization. Synthesis and experimental fitness determination of only 600 different compounds from a virtual library of more than 1017 molecules was necessary to achieve this goal.These authors contributed equally to the results presentedThese authors contributed equally to the results presentedThese authors contributed equally to the results presentedThese authors contributed equally to the results presented 相似文献