Base de dados : MEDLINE
Pesquisa : D12.776.124.486.485.114.167 [Categoria DeCS]
Referências encontradas : 655 [refinar]
Mostrando: 1 .. 10   no formato [Longo]

página 1 de 66 ir para página                         

  1 / 655 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28888872
Autor:Lee J; Kim M; Seo Y; Lee Y; Park H; Byun SJ; Kwon MH
Endereço:Department of Biomedical Sciences, Graduate School, Ajou University, 206 World Cup-ro, Yeongtong-gu, Suwon 16499, South Korea.
Título:The catalytic activity of a recombinant single chain variable fragment nucleic acid-hydrolysing antibody varies with fusion tag and expression host.
Fonte:Arch Biochem Biophys; 633:110-117, 2017 Nov 01.
ISSN:1096-0384
País de publicação:United States
Idioma:eng
Resumo:The antigen-binding properties of single chain Fv antibodies (scFvs) can vary depending on the position and type of fusion tag used, as well as the host cells used for expression. The issue is even more complicated with a catalytic scFv antibody that binds and hydrolyses a specific antigen. Herein, we investigated the antigen-binding and -hydrolysing activities of the catalytic anti-nucleic acid antibody 3D8 scFv expressed in Escherichia coli or HEK293f cells with or without additional amino acid residues at the N- and C-termini. DNA-binding activity was retained in all recombinant forms. However, the DNA-hydrolysing activity varied drastically between forms. The DNA-hydrolysing activity of E. coli-derived 3D8 scFvs was not affected by the presence of a C-terminal human influenza haemagglutinin (HA) or His tag. By contrast, the activity of HEK293f-derived 3D8 scFvs was completely lost when additional residues were included at the N-terminus and/or when a His tag was incorporated at the C-terminus, whereas a HA tag at the C-terminus did not diminish activity. Thus, we demonstrate that the antigen-binding and catalytic activities of a catalytic antibody can be separately affected by the presence of additional residues at the N- and C-termini, and by the host cell type.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies, Catalytic); 0 (Hemagglutinins); 0 (His-His-His-His-His-His); 0 (Oligopeptides); 0 (Recombinant Fusion Proteins); 0 (Single-Chain Antibodies); 4QD397987E (Histidine); 9007-49-2 (DNA)


  2 / 655 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28709828
Autor:Wenthur CJ; Cai X; Ellis BA; Janda KD
Endereço:Departments of Chemistry and Immunology, The Scripps Research Institute, La Jolla, CA 92037, United States.
Título:Augmenting the efficacy of anti-cocaine catalytic antibodies through chimeric hapten design and combinatorial vaccination.
Fonte:Bioorg Med Chem Lett; 27(16):3666-3668, 2017 08 15.
ISSN:1464-3405
País de publicação:England
Idioma:eng
Resumo:Given the need for further improvements in anti-cocaine vaccination strategies, a chimeric hapten (GNET) was developed that combines chemically-stable structural features from steady-state haptens with the hydrolytic functionality present in transition-state mimetic haptens. Additionally, as a further investigation into the generation of an improved bifunctional antibody pool, sequential vaccination with steady-state and transition-state mimetic haptens was undertaken. While GNET induced the formation of catalytically-active antibodies, it did not improve overall behavioral efficacy. In contrast, the resulting pool of antibodies from GNE/GNT co-administration demonstrated intermediate efficacy as compared to antibodies developed from either hapten alone. Overall, improved antibody catalytic efficiency appears necessary to achieve the synergistic benefits of combining cocaine hydrolysis with peripheral sequestration.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Nome de substância:0 (Antibodies, Catalytic); 0 (Haptens); 0 (Immunoglobulin G); I5Y540LHVR (Cocaine)


  3 / 655 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28674034
Autor:Bowen A; Wear M; Casadevall A
Endereço:Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Título:Antibody-Mediated Catalysis in Infection and Immunity.
Fonte:Infect Immun; 85(9), 2017 Sep.
ISSN:1098-5522
País de publicação:United States
Idioma:eng
Resumo:The existence of catalytic antibodies has been known for decades. Natural antibodies capable of cleaving nucleic acid, protein, and polysaccharide substrates have been described. Although the discovery of catalytic antibodies initially aroused great interest because of their promise for the development of new catalysts, their enzymatic performance has been disappointing due to low reaction rates. However, in the areas of infection and immunity, where processes often occur over much longer times and involve high antibody concentrations, even low catalytic rates have the potential to influence biological outcomes. In this regard, the presence of catalytic antibodies recognizing host antigens has been associated with several autoimmune diseases. Furthermore, naturally occurring catalytic antibodies to microbial determinants have been correlated with resistance to infection. Recently, there has been substantial interest in harnessing the power of antibody-mediated catalysis against microbial antigens for host defense. Additional work is needed, however, to better understand the prevalence, function, and structural basis of catalytic activity in antibodies. Here we review the available information and suggest that antibody-mediated catalysis is a fertile area for study with broad applications in infection and immunity.
Tipo de publicação: JOURNAL ARTICLE; REVIEW
Nome de substância:0 (Antibodies, Catalytic)


  4 / 655 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28075071
Autor:Shahsavarian MA; Chaaya N; Costa N; Boquet D; Atkinson A; Offmann B; Kaveri SV; Lacroix-Desmazes S; Friboulet A; Avalle B; Padiolleau-Lefèvre S
Endereço:Génie Enzymatique et Cellulaire (GEC), FRE 3580 CNRS, Université de Technologie de Compiègne, France.
Título:Multitarget selection of catalytic antibodies with ß-lactamase activity using phage display.
Fonte:FEBS J; 284(4):634-653, 2017 Feb.
ISSN:1742-4658
País de publicação:England
Idioma:eng
Resumo:ß-lactamase enzymes responsible for bacterial resistance to antibiotics are among the most important health threats to the human population today. Understanding the increasingly vast structural motifs responsible for the catalytic mechanism of ß-lactamases will help improve the future design of new generation antibiotics and mechanism-based inhibitors of these enzymes. Here we report the construction of a large murine single chain fragment variable (scFv) phage display library of size 2.7 × 10 with extended diversity by combining different mouse models. We have used two molecularly different inhibitors of the R-TEM ß-lactamase as targets for selection of catalytic antibodies with ß-lactamase activity. This novel methodology has led to the isolation of five antibody fragments, which are all capable of hydrolyzing the ß-lactam ring. Structural modeling of the selected scFv has revealed the presence of different motifs in each of the antibody fragments potentially responsible for their catalytic activity. Our results confirm (a) the validity of using our two target inhibitors for the in vitro selection of catalytic antibodies endowed with ß-lactamase activity, and (b) the plasticity of the ß-lactamase active site responsible for the wide resistance of these enzymes to clinically available inhibitors and antibiotics.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies, Catalytic); 0 (Penicillins); 0 (Peptide Library); 0 (Recombinant Proteins); 0 (Single-Chain Antibodies); 0 (beta-Lactams); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (beta-lactamase TEM-1)


  5 / 655 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:27872188
Autor:Bowen A; Wear MP; Cordero RJ; Oscarson S; Casadevall A
Endereço:From the Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461.
Título:A Monoclonal Antibody to Cryptococcus neoformans Glucuronoxylomannan Manifests Hydrolytic Activity for Both Peptides and Polysaccharides.
Fonte:J Biol Chem; 292(2):417-434, 2017 Jan 13.
ISSN:1083-351X
País de publicação:United States
Idioma:eng
Resumo:Studies in the 1980s first showed that some natural antibodies were "catalytic" and able to hydrolyze peptide or phosphodiester bonds in antigens. Many naturally occurring catalytic antibodies have since been isolated from human sera and associated with positive and negative outcomes in autoimmune disease and infection. The function and prevalence of these antibodies, however, remain unclear. A previous study suggested that the 18B7 monoclonal antibody against glucuronoxylomannan (GXM), the major component of the Cryptococcus neoformans polysaccharide capsule, hydrolyzed a peptide antigen mimetic. Using mass spectrometry and Förster resonance energy transfer techniques, we confirm and characterize the hydrolytic activity of 18B7 against peptide mimetics and show that 18B7 is able to hydrolyze an oligosaccharide substrate, providing the first example of a naturally occurring catalytic antibody for polysaccharides. Additionally, we show that the catalytic 18B7 antibody increases release of capsular polysaccharide from fungal cells. A serine protease inhibitor blocked peptide and oligosaccharide hydrolysis by 18B7, and a putative serine protease-like active site was identified in the light chain variable region of the antibody. An algorithm was developed to detect similar sites present in unique antibody structures in the Protein Data Bank. The putative site was found in 14 of 63 (22.2%) catalytic antibody structures and 119 of 1602 (7.4%) antibodies with no annotation of catalytic activity. The ability of many antibodies to cleave antigen, albeit slowly, supports the notion that this activity is an important immunoglobulin function in host defense. The discovery of GXM hydrolytic activity suggests new therapeutic possibilities for polysaccharide-binding antibodies.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies, Bacterial); 0 (Antibodies, Catalytic); 0 (Antibodies, Monoclonal); 0 (Peptides); 0 (Polysaccharides, Bacterial)


  6 / 655 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PMID:27552288
Autor:Ishikawa F; Shirahashi M; Hayakawa H; Yamaguchi A; Hirokawa T; Tsumuraya T; Fujii I
Endereço:Department of Biological Science, Graduate School of Science, Osaka Prefecture University , 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Título:Site-Directed Chemical Mutations on Abzymes: Large Rate Accelerations in the Catalysis by Exchanging the Functionalized Small Nonprotein Components.
Fonte:ACS Chem Biol; 11(10):2803-2811, 2016 Oct 21.
ISSN:1554-8937
País de publicação:United States
Idioma:eng
Resumo:Taking advantage of antibody molecules to generate tailor-made binding sites, we propose a new class of protein modifications, termed as "site-directed chemical mutation." In this modification, chemically synthesized catalytic components with a variety of steric and electronic properties can be noncovalently and nongenetically incorporated into specific sites in antibody molecules to induce enzymatic activity. Two catalytic antibodies, 25E2 and 27C1, possess antigen-combining sites which bind catalytic components and act as apoproteins in catalytic reactions. By simply exchanging these components, antibodies 25E2 and 27C1 can catalyze a wide range of chemical transformations including acyl-transfer, ß-elimination, aldol, and decarboxylation reactions. Although both antibodies were generated with the same hapten, phosphonate diester 1, they showed different catalytic activity. When phenylacetic acid 4 was used as the catalytic component, 25E2 efficiently catalyzed the elimination reaction of ß-haloketone 2, whereas 27C1 showed no catalytic activity. In this work, we focused on the ß-elimination reaction and examined the site-directed chemical mutation of 27C1 to induce activity and elucidate the catalytic mechanism. Molecular models showed that the cationic guanidyl group of Arg in 27C1 makes a hydrogen bond with the P═O oxygen in the hapten. This suggested that during ß-elimination, Arg of 27C1 would form a salt bridge with the carboxylate of 4, thus destroying reactivity. Therefore, we utilized site-directed chemical mutation to change the charge properties of the catalytic components. When amine components 7-10 were used, 27C1 efficiently catalyzed the ß-elimination reaction. It is noteworthy that chemical mutation with secondary amine 8 provided extremely high activity, with a rate acceleration [(k /K 2)/k ] of 1 000 000. This catalytic activity likely arises from the proximity effect, plus general-base catalysis associated the electrostatic interactions. In 27C1, the cationic guanidyl group of Arg is spatially close to the nitrogen of the amine components. In this microenvironment, the intrinsic pK of the amine is perturbed and shifts to a lower pK , which efficiently abstracts the α-proton during the reaction. This mechanism is consistent with the observed kinetic isotope effect (E2 or E1cB mechanism). Thus, site-directed chemical mutation provides a better understanding of enzyme functions and opens new avenues in biocatalyst research.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies, Catalytic)


  7 / 655 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:27270933
Autor:Mokrushina YA; Stepanova AV; Bobik TV; Smirnov IV; Gabibov AG
Endereço:Laboratory of Biocatalysis, M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Título:New Genetic Constructs for Generation of Stable Therapeutic Antibodies to Organophosphorus Toxins in Methylotrophic Yeasts Pichia Pastoris.
Fonte:Bull Exp Biol Med; 161(1):83-7, 2016 May.
ISSN:1573-8221
País de publicação:United States
Idioma:eng
Resumo:We propose a new method of obtaining of stable Fab-fragments of antibodies in Pichia pastoris expression system. Recently, we obtained Fab-fragments of antibodies neutralizing organophosphorus toxins. However, high yield of the target products was not attained because of high level of proteolytic degradation. In the present study, we identified sites of proteolytic degradation in Fab-fragments and endogenous proteases performing degradation, which allowed obtaining optimized genetic constructs for expression of antibody heavy chains (IgGγ1) and kappa and lambda isotypes of light chains. Co-transformation of these vectors allowed obtaining Fab-fragments of antibodies to organophosphorus toxins without proteolytic degradation of the product.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies, Catalytic); 0 (Fungal Proteins); 0 (Immunoglobulin Fab Fragments); 0 (Organophosphorus Compounds); EC 3.4.- (Peptide Hydrolases)


  8 / 655 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
PMID:27196086
Autor:Doronin VB; Parkhomenko TA; Castellazzi M; Cesnik E; Buneva VN; Granieri E; Nevinsky GA
Endereço:Novosibirsk Medical University, Ministry of Public Health of Russian Federation, Novosibirsk, Russia.
Título:Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis.
Fonte:PLoS One; 11(5):e0154688, 2016.
ISSN:1932-6203
País de publicação:United States
Idioma:eng
Resumo:We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed.
Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE
Nome de substância:0 (Antibodies, Antinuclear); 0 (Antibodies, Catalytic); 0 (Cerebrospinal Fluid Proteins); 0 (Immunoglobulin G); 0 (MBP protein, human); 0 (Myelin Basic Protein); 9007-49-2 (DNA); EC 3.2.1.- (Amylases)


  9 / 655 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:27067006
Autor:Mahendra A; Peyron I; Thaunat O; Dollinger C; Gilardin L; Sharma M; Wootla B; Rao DN; Padiolleau-Lefevre S; Boquet D; More A; Varadarajan N; Kaveri SV; Legendre C; Lacroix-Desmazes S
Endereço:Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, Unité Mixte de Recherche S1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Université Paris Descartes, Sorbon
Título:Generation of Catalytic Antibodies Is an Intrinsic Property of an Individual's Immune System: A Study on a Large Cohort of Renal Transplant Patients.
Fonte:J Immunol; 196(10):4075-81, 2016 05 15.
ISSN:1550-6606
País de publicação:United States
Idioma:eng
Resumo:Renal transplant is the treatment of choice for patients with terminal end-stage renal disease. We have previously identified low levels of catalytic IgG as a potential prognosis marker for chronic allograft rejection. The origin and physiopathological relevance of catalytic Abs is not well understood, owing to the fact that catalytic Abs have been studied in relatively small cohorts of patients with rare diseases and/or without systematic follow-up. In the current study, we have followed the evolution of the levels of catalytic IgG in a large cohort of renal transplant patients over a 2-y period. Our results demonstrate that, prior to transplant, patients with renal failure present with heterogeneous levels of IgG hydrolyzing the generic proline-phenylalanine-arginine-methylcoumarinamide (PFR-MCA) substrate. PFR-MCA hydrolysis was greater for patients' IgG than for a therapeutic preparation of pooled IgG from healthy donors. Renal transplant was marked by a drastic decrease in levels of catalytic IgG over 3 mo followed by a steady increase during the next 21 mo. Patients who displayed high levels of catalytic IgG pretransplant recovered high levels of catalytic Abs 2 y posttransplant. Interestingly, IgG-mediated hydrolysis of a model protein substrate, procoagulant factor VIII, did not correlate with that of PFR-MCA prior transplantation, whereas it did 12 mo posttransplant. Taken together, our results suggest that the level of circulating catalytic IgG under pathological conditions is an intrinsic property of each individual's immune system and that recovery of pretransplant levels of catalytic IgG is accompanied by changes in the repertoire of target Ags.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Nome de substância:0 (Antibodies, Catalytic); 0 (Autoantibodies); 0 (Biomarkers); 0 (Immunoglobulin G); 9001-27-8 (Factor VIII)


  10 / 655 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:26655427
Autor:Xia Y; Eryilmaz E; Zhang Q; Cowburn D; Putterman C
Endereço:Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: ymxia@whu.edu.cn.
Título:Anti-DNA antibody mediated catalysis is isotype dependent.
Fonte:Mol Immunol; 69:33-43, 2016 Jan.
ISSN:1872-9142
País de publicação:England
Idioma:eng
Resumo:Anti-DNA antibodies are the serological hallmark of systemic lupus erythematosus, and participate in the pathogenesis of lupus nephritis by cross-reacting with multiple renal antigens. Previously, using a panel of murine anti-DNA IgGs that share identical variable regions but that differ in the constant regions, we demonstrated that the cross-reaction and renal pathogenicity of anti-DNA antibodies are isotype dependent. In this study, we investigated the catalytic potential of this anti-DNA antibody panel, and determined its isotype dependency. The three isotype switch variants (IgG1, IgG2a, IgG2b) and the parent IgG3 PL9-11 anti-DNA antibodies were compared in their catalysis of 500 base pair linear double stranded DNA and a 12-mer peptide (ALWPPNLHAWVP), by gel analysis, MALDI-TOF mass spectrometry, and nuclear magnetic resonance spectroscopy. The binding affinity of anti-DNA antibodies to double stranded DNA and peptide antigens were assessed by ELISA and surface plasmon resonance. We found that the PL9-11 antibody isotypes vary significantly in their potential to catalyze the cleavage of both linear and double stranded DNA and the proteolysis of peptides. The degree of the cleavage and proteolysis increases with the incubation temperature and time. While different PL9-11 isotypes have the same initial attack sites within the ALWPPNLHAWVP peptide, there was no correlation between binding affinity to the peptide and proteolysis rates. In conclusion, the catalytic properties of anti-DNA antibodies are isotype dependent. This finding provides further evidence that antibodies that share the same variable region, but which have different constant regions, are functionally distinct. The catalytic effects modulated by antibody constant regions need to be considered in the design of therapeutic antibodies (abzymes) and peptides designed to block pathogenic autoantibodies.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Nome de substância:0 (Antibodies, Antinuclear); 0 (Antibodies, Catalytic); 0 (Immunoglobulin Isotypes)



página 1 de 66 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde