共查询到19条相似文献,搜索用时 125 毫秒
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以人血清白蛋白为连接剂和药物载体, 制备了人血清白蛋白-叶酸偶联物(HSA-FA), 其偶联数n≈3. 以SnCl2·H2O作为还原剂, 采用直接标记法制备 99mTc-HSA-FA标记配合物, 其放射化学纯度大于90%. 体外细胞结合实验结果表明, 99mTc-HSA-FA能被叶酸受体高表达的KB细胞特异性摄取. 荷瘤S180小鼠体内生物分布的研究结果表明, 与 99mTc-HSA相比, 99mTc -HSA-FA在小鼠体内的生物分布发生明显变化, 其在肿瘤中的放射性浓集明显增加(t=12.03, P<0.05), 并表现出较高的摄取[(4.37±1.12)%ID/g at 1 h]和滞留[(3.40±0.69)%ID/g at 4 h]; 经注射过量稳定配体使 99mTc-HSA-FA受到抑制后, 其在肿瘤和肾中的摄取明显降低(t=24.17和17.87, P<0.05), 表明人血清白蛋白-叶酸偶联物对叶酸受体有特异性结合. 相似文献
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芳香硝基物CO选择还原—环境友好芳胺合成新路线 总被引:1,自引:0,他引:1
含有羰基、氯、氰基和双键的芳胺类化合物是染料、颜料、医药和农药等领域的重要中间体[1].然而,它们难以从相应的芳香硝基物与金属氢化物试剂的催化加氢直接制得,因为在这些还原条件下,羰基、氯、氰基和双键也能发生还原反应[2] .目前,工业上通常还只能用经典的铁粉还原法或硫化碱还原法生产这些芳胺衍生物,但用铁粉还原法,产生的大量铁泥严重污染环境;硫化碱还原法,则存在合成路线复杂、成本高、收率低和废液量大等不足之处[3] .近年来,一种以CO为还原剂还原芳香硝基物的反应,以其对硝基的高选择性而日益引起人们的兴趣,因而有望成为合成含有羰基、氯和氰基的芳香胺类衍生物的一条环境友好新途径[4]. 相似文献
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发展位点特异且具有明确拓扑结构的蛋白质-高分子偶联物是高分子和化学生物学领域共同面对的挑战之一.在聚合物末端精确引入一个或多个具有特殊反应活性的生物正交官能团是实现位点特异生物偶联的关键前提.这一过程通常比较低效、需要多步骤的官能团转化、聚合后修饰以及保护脱保护,费时且繁琐.最近,通过在聚合过程中原位生成官能团,以一锅-两步的过程得到可直接用于蛋白质偶联的异遥爪聚合物,从而实现了多种不同拓扑结构的蛋白质-聚氨基酸偶联物的快速构筑.这一简洁的合成路线实现了以前尚未获得的头-尾相接的环状偶联物的制备,使这些偶联物表现出了很强的体外酶稳定性以及热稳定性.该工作是蛋白质-高分子偶联化学的一次创新的尝试;同时,利用该方法所制备的偶联物在蛋白质药物领域具有广阔的应用前景. 相似文献
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单克隆抗体(单抗)药物是发展最为迅速的一个领域,在过去25年间大约有近30个单抗药物面世,主要用于抗癌和炎症;最近一种新的抗体药物偶联物(antibody-drug conjugate,ADC)技术取得了极大的成功。ADC是通过一个特殊的化学单元将单抗和小分子药物连接起来,充分利用抗体原有的亲合性和选择性,以及小分子药物的强药效,来降低小分子药物的毒性或延长小分子化合物的半衰期。随着一些链接技术的成熟和ADC药物上市,未来ADC将成为治疗疾病的重要手段。为了成功研制出一个新的ADC,需要对单抗、小分子药物和链接进行不断优化。一些新技术的问世也将极大促进ADC的发展。 相似文献
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Natalia I. Larionov Inna P. Gladysheva Olga V. Polekhina Lidiya P. Kurochkina Elena N. Gorbatova 《Applied biochemistry and biotechnology》1996,61(1-2):139-148
The modification of Bowman-Birk soybean protease inhibitor (BBI) with the monoaldehyde derivative of block copolymer of ethylene
oxide and propylene oxide (PE),M
r
2000 is described. The conjugate contains five covalently bound polymer chains per protein molecule, and retains the ability
to inhibit trypsin and chymotrypsinlike proteinases. The distribution of native BBI and the BBI-PE conjugate was examined
in mice. After iv injection of [125I]BBI and [125I]BBIPE, both inhibitors distributed very rapidly to the liver, kidney, and lungs, and more slowly to the brain. At the same
time-points (up to 24 h), radioactivity in the blood and organs of mice injected with modified inhibitor was higher than that
of the native inhibitor. The blood concentration time profile following iv administration of two BBI preparations at a dose
3 mg/kg was reasonable well described by a two-compartment open model with first-order elimination kinetics. The total clearance
of BBI-PE decreased by a factor of 8, body mean residence time increased by a factor of 5 in comparison with BBI. A physiological
pharmacokinetic model was developed to describe the tissue-to-blood distribution of two inhibitors. One-compartment physiological
organ model (flow limited) was used to describe of timecourse profiles of BBI concentration in organs. A two-compartment physiological
organ model (membrane limited) was used to predict tissue-to-blood distribution of conjugated BBI in some organs of mice (liver,
lungs). The predicted concentration curves of BBI and BBI-PE in blood and organs in mice (with the exception of kidney) showed
good agreement with the observed values. 相似文献
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The preparation of isonipecotinoyl analogues of aminopterin and methotrexate is described. Condensation of diethyl N-isonipecotinoyl-L-glutamate 4 with 2-amino-5-bromomethyl-3-cyanopyrazine 5 afforded diethyl N-(N-[(2-amino-3-cyanopyrazin-5-yl)methyl]isonipecotinoyl)-L-glutamate 6 . Cyclisation of 6 with guanidine followed by blocking group hydrolysis afforded N-([N-(2,4-diaminopteridin-6-yl)methyl]isonipecotinoyl)-L-glutamic acid 8 . Coupling of N-(2-amino-4(3H)ioxopteridin-6-yl]methyl)isonipecotinic acid 11 with diethyl L-glutamate gave diethyl N-[(N-[2-amino-4(3H)-oxopteridin-6-yl]methyl)isonipecotinoyl]-L-glutamate 12 . Blocking group hydrolysis afforded N-[(N-[2-amino-4(3H)-oxopteridin-6-yl]methyl)isonipecotinoyl]-L-glutamic acid 13 . 相似文献
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A heteroenzyme conjugate retaining activities of two component enzymes from trypsin and chymotrypsin was prepared using N-succinimidyl
pyridyl dithiopropionate as crosslinking reagent. The conjugate bound to both trypsin and chymotrypsin affinity columns. Trypsin
and chymotrypsin were linked in the ratio of 1:1 on mol basis. The conjugate, when treated with dimethyladipimidate, showed
decreased autolysis of its trypsin component. 相似文献
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Antonio ArcadiOrazio A. Attanasi Gianluca GiorgiPaolino Filippone Elisabetta RossiStefania Santeusanio 《Tetrahedron letters》2003,44(46):8391-8394
1,2-Diaza-1,3-butadienes reacted with rhodanine affording 2-(mercaptoacetyl)iminothiazoline derivatives through conjugate addition/annulation/ring-opening/oxidative dimerization. The hypothesized ring-closure and ring-opening mechanism was supported by X-ray crystal structure analysis of a compound obtained by reaction of the same reagents with a chiral 1,3-oxazolidine-2-thione derivative. 相似文献
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G. D. Kolomnikova T. O. Krylova I. V. Chernoglazova P. V. Petrovskii Yu. G. Gololobov 《Russian Chemical Bulletin》1993,42(7):1188-1190
In the presence of trifluoroacetic acid, ethyl 2-cyanoacrylate readily reacts with nucleophilic reagents, such as 2-chloro-1,3,2-benzodioxaphosphole, (EtO)3P, (EtO)2PCl, Ph2PCl, Ph3P, and thiourea. In these reactions the acid proton enters position 2 of the cyanoacrylate, whereas the nucleophilic component enters position 3, in accordance with the electron density distribution in the acrylate. In the absence of trifluoroacetic acid the above reagents, except 2-chloro-1,3,2-benzodioxaphosphole, cause ethyl 2-cyanoacrylate polymerization. The interaction of ethyl 2-cyanoacrylate with 2-chloro-1,3,2-benzodioxaphosphole and trifluoroacetic acid is the first example of a 2-cyanoacrylate taking part in the acid-initiated electrophilic conjugate addition of a weak nucleophile.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1245–1247, July, 1993. 相似文献
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Novel fluconazole/bile acid conjugates were designed and their regioselective synthesis was achieved in very high yield via Cu(I) catalyzed intermolecular 1,3-dipolar cycloaddition. These new molecules showed good antifungal activity against Candida species. 相似文献