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ChemElectroChem · 2017 ·Vol. 4 ·期 3 ·472-475 · IF 4.136

A Peptide-Based Electrochemical Biosensor for Facile Measurement of Whole-Blood Heparin

Fanyu Meng,Weiguo Liang,Haixuan Sun,Ligang Wu,Xiao Gong,Peng Miao

Graphical Peptide–heparin composites : A simple electrochemical approach for the determination of heparin level in human whole-blood is developed based on specific peptide recognition (see picture). The first peptide-based electrochemical biosensor for the measurement of the anti-coagulant heparin using electrochemical impedance spectroscopy is reported. The peptide immobilized on the electrode interface specially captures heparin with high affinity. The composites formed on the electrode can thus effectively repel electrochemical species, leading to an increase in interfacial charge transfer resistance. After analyzing the electrochemical signals, a linear detection range from 0.05 to 10.0 μg/mL is obtained. The detection limit is calculated to be 0.01 μg/mL, which is extremely low with such a simple sensing mechanism. Moreover, the proposed method has potential application for sensitive and separation-free detection of heparin in whole-blood samples.

研究领域: 生物化学 · 医学检测 · 电化学
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2021 · IF 3.205

Development and validation of an ultra-high performance liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of direct oral anticoagulants in human plasma

Yu-Fei Zhang,Xiao-Qin Liu,Yang Wang,Xin Xu,Ming-Kang Zhong,Pu Zhang,Chun-Lai Ma

Direct oral anticoagulants are widely used to treat and prevent thromboembolic disorders. With rising clinical application, monitoring concentrations of direct oral anticoagulants are necessary in certain clinical conditions. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of dabigatran etexilate, dabigatran, rivaroxaban, edoxaban, and apixaban, in human plasma. Protein precipitation with methanol was performed for sample preparation. The direct oral anticoagulants and internal standards were separated under gradient conditions using a C18 column, at an analytical run time of 8 min. The mobile phase was composed of 0.1% (v/v) formic acid in water (solvent A) and 0.1% (v/v) formic acid in acetonitrile (solvent B) at a flow rate of 0.3 mL/min. Mass detection was performed in multiple reaction monitoring using positive ionization mode. The method was validated over a range of 1.0–500 ng/mL for dabigatran etexilate, 0.1–500 ng/mL for dabigatran, and 0.5–500 ng/mL for edoxaban, rivaroxaban, and apixaban. The method detection limits of five analytes were in the range of 0.05–0.5 ng/mL. The lower limits of quantification of five analytes ranged from 0.1 to 1 ng/mL. The linearity (r 2 values) was higher than 0.997. The accuracy of the low, medium, and high quality control samples were between 85.9 and 114%, and intra- and inter-day precision were below 9.47%. This validated method was successfully used to determine the plasma concentrations of rivaroxaban in 32 patients, and of dabigatran etexilate and dabigatran in 1 patient.

研究领域: 临床药理学 · 分析化学
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CARBOHYDRATE POLYMERS · 2020 · IF 7.182

Anticoagulant chitosan-kappa-carrageenan composite hydrogel sorbent for simultaneous endotoxin and bacteria cleansing in septic blood

Yupei Li,Jiameng Li,Zhenqiang Shi,Yilin Wang,Xin Song,Liya Wang,Mei Han,Heyue Du,Chao He,Weifeng Zhao,Baihai Su,Changsheng Zhao

Here, we describe a green approach to fabricate genipin crosslinked chitosan-kappa-carrageenan composite hydrogels (C-K hydrogels) aiming at reducing endotoxin level and bacteria burden in septic blood synchronously. The chemical compositions and morphologies of the developed C-K hydrogels were characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy. The C-K hydrogels significantly inhibited adverse blood-material interactions such as hemolysis, complement activation, platelet activation and contact activation, and exhibited better anticoagulant properties than raw chitosan hydrogels. Most importantly, the optimized C 2 -K 1 hydrogels were competent to eliminate 63.3 % of endotoxin in septic blood with a maximum adsorption capacity of 95.0 EU/g during a 3-h simulative hemoperfusion procedure. Bacteria cleansing experiments further demonstrated that the optimized C 2 -K 1 hydrogels effectively decreased 46.0 % of E. coli and 68.7 % of S. aureus load, respectively. It is believed that the C-K hydrogels are promising hemoperfusion sorbents to treat severe septic patients.

研究领域: 生物材料 · 生物医学工程 · 血液学
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BIOMACROMOLECULES · 2019 · IF 5.667

Synthesis and Properties of Functional Glycomimetics through Click Grafting of Fucose onto Chondroitin Sulfates

Fei Fan,Ping Zhang,Lihao Wang,Tiantian Sun,Chao Cai,Guangli Yu

Fucosylated chondroitin sulfate (fCS), a representative marine polysaccharide isolated from sea cucumber, possesses diverse biological functions especially as a promising anticoagulant. However, its supply suffers from the challenges of high-cost materials, different species, and batch-to-batch variability. In the present study, we designed a concise route for the synthesis of functional glycomimetics by natural fCS as a template. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride-mediated amidation was applied on chondroitin sulfates for site-selective alkynylation with controllable ratios between 0.15 and 0.78. A small library of 12 fCS glycomimetics with specific sulfation patterns and fucose branches was prepared through copper-catalyzed azide–alkyne cycloaddition, which was fully characterized by nuclear magnetic resonance spectroscopy and size-exclusion chromatography with multiangle light scattering and refractive index. Through screening of their biological activities, CSE-F1 and CSE-SF1 exhibited anticoagulant activities through intrinsic pathway and inhibition of factor Xa by antithrombin III. The concise approach developed herein supplies novel glycopolymers to mimic the distinct functions of natural polysaccharides and promote the development of marine carbohydrate-based drugs.

研究领域: 海洋化学 · 药学 · 碳水化合物化学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2021 · IF 6.953

Prolonged release and shelf-life of anticoagulant sulfated polysaccharides encapsulated with ZIF-8

Jie Zheng,Bingzhi Li,Yuan Ji,Yin Chen,Xun Lv,Xing Zhang,Robert J. Linhardt

Natural active polysaccharides are attracting increased attention from pharmaceutical industries for their valuable biological activities. However, the application of polysaccharides has been restricted due to their relatively large molecular weight, complex structure, and instability. Metal-organic frameworks (MOFs) have emerged to help deliver cargo to specific locations, achieving the objectives of eliminating the potential damage to the body, protecting the drugs, and improving therapeutic effectiveness. Here, a pH-responsive zeolitic imidazolate framework (ZIF-8) was synthesized to encapsulated three sulfated polysaccharides (heparin, fucan sulfate, fucosylated chondroitin sulfate) and a non-sulfated polysaccharide, hyaluronic acid. The resulting [email protected] biocomposites showed differences in terms of morphology, particle size, encapsulation, and release efficiency. These biocomposites retained antithrombotic activity and the framework ZIF-8 effectively protected these polysaccharides from degradation and prolonged shelf-life of the anticoagulants from the unfavorable environment.

CAS / MDL: 3326-32-7 693-98-1
研究领域: 药学 · 材料科学 · 药物递送系统
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