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111.
利用纳米材料制作多肽疫苗佐剂的思考 总被引:11,自引:0,他引:11
纳米粒子与生物体有着密切的关系,DNA/蛋白质复合体就在15~20 nm之间,多种病毒颗粒也是纳米级的超微粒子.多肽抗原需要与适当载体形成复合物才能诱导有效的免疫应答,但载体效应难以避免.纳米佐剂可以避免载体效应的发生,而且还是巨噬细胞(Mφ)、树突状细胞(DC)的首选吞噬目标.纳米化的有机药物可提高其生物利用度、制剂的均匀性、分散性和吸收性;脂质体可使药物更快地到达靶向部位,而且特异性更强.目前主要用理化的方法制作纳米材料,几乎所有的生化药品,特别是DNA药物的研究开发都可引入纳米材料,多肽疫苗的分子佐剂更是如此. 相似文献
112.
113.
Paliakkara L. Jaison Vadakkedath M. Kannan Mandagini Geetha Padinjaradath S. Appukuttan 《Journal of biosciences》1993,18(2):187-193
Naturally occurring serum IgG against terminal α-galactoside epitopes (anti-Gal), present exclusively in man, apes and old
world monkeys, was used as probe for these epitopes in human brain. Human brain grey matter soluble glycoproteins enriched
inα galactosyl groups by affinity chromatography on jacalin-sepharose, specifically binds to human anti-Gal in immuno dot
blots. Anti-Gal recognized exclusively the terminal α galactoside epitope in human brain glycoproteins since binding was abolished
by the presence of 1-0-methyl α-D-galactopyranoside as well as by pretreatment of glycoproteins with coffee bean α-galactosidase.
Anti-Gal-peroxidase staining of jacalin-binding human brain glycoproteins in western immuno blots revealed mainly five anti-Gal-binding
polypeptides withM
r
(in kDa) of 94, 108, 180, 210 and 230 respectively. Since the presence of anti-Gal in higher animals accompanies suppression
of the corresponding epitope in most tissues, apparently to maintain immunological balance, possible implications of the above
observation for autoimmunity, tumor metastasis and infection are discussed. 相似文献
114.
115.
T. Noelle Lombana Jack Bevers III Amy M. Berkley Evangeline Toy Ryan Cook 《MABS-AUSTIN》2019,11(1):75-93
As an immune evasion strategy, MICA and MICB, the major histocompatibility complex class I homologs, are proteolytically cleaved from the surface of cancer cells leading to impairment of CD8 + T cell- and natural killer cell-mediated immune responses. Antibodies that inhibit MICA/B shedding from tumors have therapeutic potential, but the optimal epitopes are unknown. Therefore, we developed a high-resolution, high-throughput glycosylation-engineered epitope mapping (GEM) method, which utilizes site-specific insertion of N-linked glycans onto the antigen surface to mask local regions. We apply GEM to the discovery of epitopes important for shedding inhibition of MICA/B and validate the epitopes at the residue level by alanine scanning and X-ray crystallography (Protein Data Bank accession numbers 6DDM (1D5 Fab-MICA*008), 6DDR (13A9 Fab-MICA*008), 6DDV (6E1 Fab-MICA*008). Furthermore, we show that potent inhibition of MICA shedding can be achieved by antibodies that bind GEM epitopes adjacent to previously reported cleavage sites, and that these anti-MICA/B antibodies can prevent tumor growth in vivo. 相似文献
116.
117.
Sophie Front Sofia Almeida Vincent Zoete Julie Charollais-Thoenig Estelle Gallienne Céline Marmy Vincent Pilloud Roger Marti Tim Wood Olivier R. Martin Stéphane Demotz 《Bioorganic & medicinal chemistry》2018,26(20):5462-5469
(5aR)-5a-C-pentyl-4-epi-isofagomine 1 is a powerful inhibitor of lysosomal β-galactosidase and a remarkable chaperone for mutations associated with GM1-gangliosidosis and Morquio disease type B. We report herein an improved synthesis of this compound and analogs (5a-C-methyl, pentyl, nonyl and phenylethyl derivatives), and a crystal structure of a synthetic intermediate that confirms its configuration resulting from the addition of a Grignard reagent. These compounds were evaluated as glycosidase inhibitors and their potential as chaperones for mutant lysosomal galactosidases determined. Based on these results and on docking studies, the 5-C-pentyl derivative 1 was selected as the optimal structure for further investigations: this compound induces the maturation of mutated β-galactosidase in fibroblasts of a GM1-gangliosidosis patient and promote the decrease of keratan sulfate and oligosaccharide load in patient cells. Compound 1 is clearly capable of restoring β-galactosidase activity and of promoting maturation of the protein, which should result in significant clinical benefit. These properties strongly support the development of compound 1 for the treatment of GM1-gangliosidosis and Morquio disease type B patients harboring β-galactosidase mutations sensitive to pharmacological chaperoning. 相似文献
118.
Epitope imprinting of iron binding protein of Neisseria meningitidis bacteria through multiple monomers imprinting approach
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Neha Gupta Roop Shikha Singh Kavita Shah Rajniti Prasad Meenakshi Singh 《Journal of molecular recognition : JMR》2018,31(7)
Epitope imprinting is a promising technique for fabrication of novel diagnostic tools. In this study, an epitope imprinted methodology for recognition of target epitope sequence as well as targeted protein infused by bacterial infection in blood samples of patients suffering from brain fever is developed. Template sequence chosen is a ferric iron binding fbp A protein present in Neisseria meningitidis bacteria. To orient the imprinting template peptide sequence on gold surface of electrochemical quartz crystal microbalance (EQCM), thiol chemistry was utilized to form the self‐assembled monolayer on EQCM electrode. Here, synergistic effects induced by various noncovalent interactions extended by multiple monomers (3‐sulfopropyl methacrylate potassium‐salt and benzyl methacrylate) were used in fabricating the imprinting polymeric matrix with additional firmness provided by N,N‐methylene‐bis‐acrylamide as cross‐linker and azo‐isobutyronitrile as initiator. Extraction of template molecule was carried out with phosphate buffer solution. After extraction of epitope molecules from the polymeric film, epitope molecularly imprinted polymeric films were fabricated on EQCM electrode surface. Nonimprinted polymers were also synthesized in the similar manner without epitope molecule. Detection limit of epitope molecularly imprinted polymers and imprinting factor (epitope molecularly imprinted polymers/nonimprinted polymers) was calculated 1.39 ng mL?1 and 12.27 respectively showing high binding capacity and specific recognition behavior toward template molecule. Simplicity of present method would put forward a fast, facile, cost‐effective diagnostic tool for mass health care. 相似文献
119.
Identification of protective determinants from microbial proteins is a necessary step in the rational design of subunit vaccines.
We have previously used a synthetic peptide scan (Pepscan) assay to map a panel of eight neutralizing monoclonal antibodies
(mAb; designated as C1.1 to C1.8) to a common motif sequence from Chlamydia trachomatis. In the present study, five of the eight mAbs were used to screen phage random peptide libraries. mAbs C1.1 and C1.3 selected
a motif sequence of G-L-X-N-D from a pIII-based phage random peptide library and a motif sequence of G-X-X-N-D from a pVIII-based
random peptide library while mAbs C1.6 to C1.8 failed to select recognizable motifs from either of the phage libraries. However,
C1.6 to C1.8 bound to the same motif sequence displayed on phage when the appropriate conformational constraints were imposed
onto the motif sequence. Thus the specificity of the mAbs identified on Pepscan assays correlates with the mAbs’ dependence
on local epitope constraints displayed on the phage surface.
Received 12 August 1996/ Accepted in revised form 03 November 1996 相似文献
120.
Pro region engineering of nerve growth factor by deep mutational scanning enables a yeast platform for conformational epitope mapping of anti‐NGF monoclonal antibodies
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