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991.
Taichi Hamanaka Keiko Nishizawa Yuji Sakasegawa Hiroshi Kurahashi Ayumi Oguma Kenta Teruya Katsumi Doh-ura 《Biochemistry and Biophysics Reports》2015
No remedies for prion disease have been established, and the conversion of normal to abnormal prion protein, a key event in prion disease, is still unclear. Here we found that substances in beetle grub hemolymph, after they were browned by aging for a month or heating for hours, reduced abnormal prion protein (PrP) levels in RML prion-infected cells. Active anti-prion components in the hemolymph were resistant to protease treatment and had molecular weights larger than 100 kDa. Aminoguanidine treatment of the hemolymph abolished its anti-prion activity, suggesting that Maillard reaction products are enrolled in the activity against the RML prion. However, levels of abnormal PrP in RML prion-infected cells were not decreased by incubation with the Maillard reaction products formed by amino acids or bovine serum albumin. The anti-prion components in the hemolymph modified neither cellular or cell-surface PrP levels nor lipid raft or autophagosome levels. The anti-prion activity was not observed in cells infected with 22 L prion or Fukuoka-1 prion, suggesting the anti-prion action is prion strain-dependent. Although the active components of the hemolymph need to be further evaluated, the present findings imply that certain specific chemical structures in the hemolymph, but not chemical structures common to all Maillard reaction products, are involved in RML prion formation or turnover, without modifying normal PrP expression. The anti-prion components in the hemolymph are a new tool for elucidating strain-dependent prion biology. 相似文献
992.
Egor Trilisky Ronald Gillespie Timothy D. Osslund Suresh Vunnum 《Biotechnology progress》2011,27(4):1054-1067
Crystallization holds the potential to be used for protein purification and low‐viscosity drug substance and drug product formulations. Twenty‐two different proteins (20 monoclonal antibodies and two Fc‐fusions) were examined to determine the breadth of applicability of crystallization to these therapeutic proteins. Vapor diffusion technique and an evaporative screening method were used to identify crystallization conditions using around a 100 initial conditions based on reagents that are generally regarded as safe (GRAS). Of 16 IgG2s examined, at least four formed diffraction‐quality crystals and four others formed crystal‐like particles. At least three of the IgG2s that crystallized well were also crystallized under the same set of operating conditions using inexpensive GRAS reagents. The crystals were formed to high‐yields in a few hours and were dissolved quickly without impacting product quality. Although only a fraction of the proteins examined crystallized, all exhibited liquid‐liquid phase separation (LLPS), which could be used for their concentration or possibly purification. One of the Fc‐fusions, for example, was concentrated by LLPS to a self‐buffering solution at 150 g/L. Crystallization and LLPS in the salting‐in region were shown to be feasible. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011 相似文献
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994.
Yewang Zhang Dengchao Li Shulai Liu Qingxun Song 《Biocatalysis and Biotransformation》2013,31(1):59-64
Enzymatic synthesis of cefaclor by penicillin acylase (PA) was carried out under kinetic control with in situ product removal (ISPR). We present a continuous acyl donor feeding strategy for enzymatic reactions. Using this strategy, the conversion of the antibiotic nucleus was improved from 65 to 91%, and the hydrolysis of phenylglycine methyl ester (PGME) was decreased. Side product (phenylglycine) production was less than half of that in the control batch. The ratio of synthesis to hydrolysis (S/H) in the process was kept stable for longer and at a higher level than in the control. This is a practical method for enzymatic synthesis of cefaclor. 相似文献
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998.
Houhou Huang Fei Han Shanshan Guan Mengdan Qian Yongfeng Wan Yaming Shan 《Journal of biomolecular structure & dynamics》2019,37(5):1360-1374
Glycoside hydrolase cellulase family 6 from Trichoderma reesei (TrCel6A) is an important cellobiohydrolase to hydrolyze cellooligosaccharide into cellobiose. The knowledge of enzymatic mechanisms is critical for improving the conversion efficiency of cellulose into ethanol or other chemicals. However, the process of product expulsion, a key component of enzymatic depolymerization, from TrCel6A has not yet been described in detail. Here, conventional molecular dynamics and steered molecular dynamics (SMD) were applied to study product expulsion from TrCel6A. Tyr103 may be a crucial residue in product expulsion given that it exhibits two different posthydrolytic conformations. In one conformation, Tyr103 rotates to open the ?3 subsite. However, Tyr103 does not rotate in the other conformation. Three different routes for product expulsion were proposed on the basis of the two different conformations. The total energy barriers of the three routes were calculated through SMD simulations. The total energy barrier of product expulsion through Route 1, in which Tyr103 does not rotate, was 22.2 kcal·mol?1. The total energy barriers of product expulsion through Routes 2 and 3, in which Tyr103 rotates to open the ?3 subsite, were 10.3 and 14.4 kcal·mol?1, respectively. Therefore, Routes 2 and 3 have lower energy barriers than Route 1, and Route 2 is the thermodynamically optimal route for product expulsion. Consequently, the rotation of Tyr103 may be crucial for product release from TrCel6A. Results of this work have potential applications in cellulase engineering. 相似文献
999.
《MABS-AUSTIN》2013,5(5):1163-1177
Remsima® (infliximab) was recently approved as the world's first biosimilar monoclonal antibody (mAb) in both the European Union and Korea. To achieve this, extensive physicochemical characterization of Remsima® in relation to Remicade® was conducted in order to demonstrate the highly similar properties between the two molecules. A multitude of state-of-the-art analyses revealed that Remsima® has identical primary as well as indistinguishable higher order structures compared with the original product. Monomer and aggregate contents of Remsima® were also found to be comparable with those of Remicade®. In terms of charge isoforms, although Remsima® was observed to contain slightly less basic variants than the original antibody, the difference was shown to be largely due to the presence of C-terminal lysine. On the other hand, this lysine was found to be rapidly clipped inside serum in vitro and in vivo, suggesting it has no effect on the biological potency or safety of the drug. Analysis of the glycan contents of the antibodies showed comparable glycan types and distributions. Recent results of clinical studies have further confirmed that the two antibody products are highly similar to each other. Based on this research as well as previous clinical and non-clinical comparability studies, Remsima® can be considered as a highly similar molecule to Remicade® in terms of physicochemical properties, efficacy, and safety for its final approval as a biosimilar product to Remicade®. 相似文献
1000.