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Ruirui Li Pengfei Gu Xiangyu Fan Junyu Shen Yulian Wu Lixuan Huang Qiang Li 《Applied biochemistry and biotechnology》2018,185(1):233-247
Single-chain variable fragment (scFv) antibodies as therapeutic agents have the potential to reduce the production cost and immunogenicity relative to monoclonal antibodies, but their monovalency and lack of a fragment crystallizable region can lead to reduced function. Multimerization is one strategy for recovering the function; however, their application is limited by the production of multimeric proteins. In our previous study, an anti-lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) scFv showed potential use in diagnosis and therapy of atherosclerotic diseases, but is limited by its inherent low antigen-binding activity. In this study, to improve the efficacy of the anti-LOX-1 scFv, we constructed the anti-LOX-1 scFv multimers by modifying the linker length between the variable domains of the scFv or by fusing the scFv with self-merization domains and expressed these scFv multimers in Brevibacillus choshinensis hosts. After optimization, all of the scFv multimers obtained efficient secretion expression. Compared with the scFv monomer, the multimers that are successfully fractionated displayed increased neutralization activity and showed elevated antigen-binding avidity, especially the tetramer, which improved the antigen avidity by two orders of magnitude. Moreover, the scFv dimer and the tetramer both displayed better stability and longer half-life in serum, which can be attractive candidates for the next-generation anti-LOX-1 therapeutic antibody. 相似文献
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Alexey V. Dobrydnev Bohdan V. Vashchenko Yulian M. Volovenko 《Tetrahedron letters》2018,59(16):1581-1582
We report the short and the simplest strategy for the synthesis of methyl 4-amino-2,2-dioxo-2,5-dihydro-1,2λ6-oxathiole-3-carboxylates bearing aliphatic substituents at the 5th position. A number of cyanohydrins were forced to react with methyl 2-(chlorosulfonyl)acetate to give the interim methyl 2-[(cyanomethoxy)sulfonyl]acetates that upon Et3N-mediated conditions underwent the CSIC [Carbanion mediated Sulfonate (Sulfonamido) Intramolecular Cyclization] reaction yielding the 5,5-disubstituted and spiranic methyl 4-amino-2,2-dioxo-2,5-dihydro-1,2λ6-oxathiole-3-carboxylates. 相似文献
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Wu Y Yu H Wang Y Huang L Tao Y Chen D Peng D Liu Z Yuan Z 《Journal of chromatography. A》2007,1146(1):1-7
A method of high-performance liquid chromatography with UV detection has been established for simultaneous quantitative determination of quinoxaline-2-carboxylic acid (QCA) and methyl-3-quinoxaline-2-carboxylic acid (MQCA), the marker residues for carbadox (CBX) and olaquindox (OLA), respectively, in the muscles and livers of porcine and chicken and in the muscle of fish. Tissue samples were subject to acid hydrolysis followed by liquid-liquid extraction and Oasis MAX solid-phase extraction clean-up. The method was validated according to the EU Commission Decision 2002/657/EC. The decision limits (CCalpha) were 0.7-2.6microg/kg and the detection capabilities (CCbeta) were 1.3-5.6microg/kg for QCA and MQCA in tissues. The recoveries of QCA and MQCA, spiked at levels of 2-100microg/kg, were from 70 to 110%; the relative standard deviation values were <20%. This simple, fast and economic method could be applied to the monitoring for the possible misuse of CBX and OLA in animal edible tissue samples. 相似文献
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Rustam T. Iminov Andrey A. Tolmachev Yulian M. Volovenko Oleg V. Shishkin 《Tetrahedron》2009,65(41):8582-586
The reaction of 2-aminobenzamides with 2-oxocyclopentane-, 2-oxocyclohexane-, and 2-oxocycloheptaneacetic acids esters was found to give 7a,8,9,10-tetrahydrocyclopenta[2,3]pyrrolo[1,2-a]quinazoline-6,12(7H,11H)-diones, 7,7a,8,9,10,11-hexahydro-6H-indolo[1,7a-a]quinazoline-6,13(12H)-diones, and 7a,8,9,10,11,12-hexahydrocyclohepta[2,3]pyrrolo[1,2-a]quinazoline-6,14(7H,13H)-diones, respectively. The relative configuration with the cis-fused butyrolactam and cycloalkane rings was assigned to the prepared compounds on the basis of an X-ray crystallographic study. 相似文献
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A broadband metamaterial absorber with high absorption simultaneously in mid-wave infrared (MWIR) and long-wave infrared (LWIR) was proposed. In the MWIR, the absorption higher than 0.8 is from 4 to 6.3 µm, while the absorption in the LWIR is from 8.7 and 9.6 µm. The absorber is insensitive to the incident angle. The broadband absorption in the MWIR is due to the slow-light effect of the trapezoid multilayered grating structure. And the broadband absorption in the LWIR is due to the phonon polariton resonant of trapezoid SiO2 layer. In the broadband high absorption region, the atmosphere is transparent, which may greatly promote the practical application of the absorber in double-color IR imaging, detecting, infrared stealth and thermal emitting. 相似文献
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通过检索古籍文献,整理了明代(公元1368—1644年)长江流域人口大量死亡事件(mass death events,MDE)10 a尺度的频次与县次序列,利用自然断点分级法、空间分析法等分析了MDE的时空特征及发生原因。结果表明:276 a间,长江流域有158 a发生MDE,明代后期发生频次和影响规模最大;季节上,表现为夏季多发(44.3%),春、秋季次之;空间上,集中分布于长江中下游、尤其是长江三角洲地区,且呈从各省交界处向各省中心扩散的趋势。“未记录原因的饥荒”和“旱灾+其他灾害-饥荒”是造成明代长江流域MDE的主要原因。气候冷干期发生频次多,影响范围广,暖湿期相反,与温度和湿度呈显著负相关;人口规模和社会脆弱程度是主要的社会影响因素。在人口规模大和社会脆弱的明代后期,MDE发生频次高,波及范围广,是气候变化与社会因素共同作用的结果。 相似文献
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Rustam T. Iminov Anton V. Tverdokhlebov Andrey A. Tolmachev Yulian M. Volovenko Svetlana V. Shishkina Oleg. V. Shishkin 《Tetrahedron》2012,68(14):3098-3102
Heating of N-{2-[(R-amino)carbonyl]phenyl}prolinamides in triethyl orthoformate solution was found to give 6-R-5,6,6a,8,9,10,10a,11-octahydropyrrolo[1′,2′:3,4]imidazo[1,2-a]quinazoline-5,11-diones. Similar reaction of N-{2-[(R-amino)carbonyl]phenyl}thiazolidine-4-carboxamides afforded 6-R-5,6,6a,10,10a,11-hexahydrothiazolo[3′,4′:3,4]imidazo[1,2-a]quinazoline-5,11-diones. The relative configuration of C-6a and C-10a centres of the tetracyclic compounds obtained was assigned as trans on the basis of X-ray crystallographic study. 相似文献