Abstract
We show for the first time ever how one mAb (mAb-5) has polyreactive (protease, DNase, and RNase) catalytic activities (catAbs). Amino acid sequence analysis of the encoded variable-genes showed that the light chains of the hybridomas expressed the germline family genes V kappa 1A, bb1.1 and V kappa...
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PMID: 20356628
PDF is available here.
Abstract
Individuals infected with HIV-1 and nearly everyone vaccinated with HIV-1 vaccines will, in time, generate antibodies against viral proteins. These antibodies do not resolve natural infection, and vaccine candidates that successfully stimulate the production of high titers of neutralizing antibodies...
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PMID: 20425053
PDF is available here.
Abstract
In human patients with autoimmune, viral, and bacterial diseases, the generation of antibodies (Abs) to foreign antigens and/or autoantibodies to self-antigens usually occurs. Some Abs with different catalytic activities (abzymes, Abzs) may be induced spontaneously by primary antigen...
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PMID: 20602079
PDF is available here.
Abstract
From the previously examined patients with ischemic heart disease (IHD), the authors formed two groups in whom an original method was used to detect the abnormal lipid-oxidizing anti-Chlamydia antibodies abzymes that increased the serum concentration of malondialdehyde. The effects of the statin ros...
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PMID: 19824403
PDF is available here.
Abstract
We demonstrated that autoantibodies (AAb) in multiple sclerosis (MS) reveal site-specific binding and cleavage toward myelin basic protein (MBP) epitope library. We have found several fragments of MBP immunodominant in terms of AAb binding. Here, we applied these peptides to DA rats with induced pro...
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PMID: 19811302
PDF is available here.
Abstract
We discuss the possible pathological process induced by DNA-cleaving Ab in the nucleus, where these Ab may induce apo. Apo processes, e.g., induced by DNA-hydrolyzing Ab, may underlie a number of syndromes observed in autoimmunity thus providing the grounds for the pathological role of DNA-hydrolyzi...
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PMID: 19811301
PDF is available here.
Abstract
The development of a novel method to attenuate bacterial virulence is reported, which is based upon the use of designed transition-state analogues to select human catalytic antibodies capable of degrading bacterial quorum-sensing molecules.
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PMID: 19283283
PDF is available here.
Abstract
It was shown that IgGs purified from the sera of healthy Wistar rats contain several different bound Me2+ ions and oxidize 3,3'-diaminobenzidine through a H2O2-dependent peroxidase and H2O2-independent oxidoreductase activity. IgGs have lost these activities after removing the internal metal ions by...
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PMID: 18837443
PDF is available here.
Abstract
We generated antibodies that hydrolyze the octanoyl moiety of ghrelin to form des-acyl ghrelin. The most proficient antibody catalyst, GHR-11E11, was found to display a second-order rate constant of 18 M(-1) x s(-1) for the hydrolysis of ghrelin to des-acyl ghrelin. I.v. administration of GHR-11E11...
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PMID: 18981425
PDF is available here.
Abstract
The prevention of many infectious diseases, allergies, autoimmune diseases, and cancer continues to be a challenge in the twenty-first century. Nonetheless, considerable advances have already been made, such as the eradication of certain infectious diseases and effective control of many others, and...
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PMID: 19100177
PDF is available here.
Abstract
In this work, rabbits were immunized with a high polymer DNA complexed with methylated BSA (mBSA) and by mBSA. It is shown that electrophoretically homogeneous preparations of polyclonal antibodies (Ab) from non-immunized rabbits and animals immunized by mBSA do not exhibit catalytic activity. Ab fr...
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PMID: 19120029
PDF is available here.
Abstract
Immunoglobulins IgG and sIgA actively hydrolyzing histone H1 have been detected on analyzing proteolytic activity of antibodies isolated by chromatography on Protein A-agarose from blood serum of patients with multiple sclerosis and from colostrum of healthy mothers. These antibodies hydrolyze other...
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PMID: 18774943
PDF is available here.
Abstract
We have shown for the first time that immunization of healthy rabbits with RNase A conjugated with BSA produces a better immune response than immunization with pure RNase and induced IgGs with RNase and DNase activities, which were intrinsic properties of IgGs, while polyclonal IgGs (pIgGs) from non...
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PMID: 18550584
PDF is available here.
Abstract
Ligand binding to enzymes and antibodies is often accompanied by protein conformational changes. Although such structural adjustments may be conducive to enzyme catalysis, much less is known about their effect on reactions promoted by engineered catalytic antibodies. Crystallographic and pre-steady...
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PMID: 18417480
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Abstract
Immunoglobulins (Igs) in uninfected humans recognize residues 421-433 located in the B cell superantigenic site (SAg) of the HIV envelope protein gp120 and catalyze its hydrolysis by a serine protease-like mechanism. The catalytic activity is encoded by germline Ig variable (V) regio...
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PMID: 18558365
PDF is available here.
Abstract
We have described FVIII-hydrolyzing IgG in 50% of inhibitor-positive patients with severe hemophilia A that inactivate therapeutic FVIII. In this study, we investigated the presence of autoimmune FVIII-hydrolyzing IgG in patients with acquired hemophilia. Pooled IgG from healthy donors demonstrated...
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PMID: 18490775
PDF is available here.
Abstract
Phage-displayed peptides that selectively bind to aldolase catalytic antibody 93F3 when bound to a particular 1,3-diketone hapten derivative have been developed using designed selection strategies with libraries containing 7-12 randomized amino acid residues. These phage-displayed peptides discrimin...
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PMID: 18472269
PDF is available here.
Abstract
We have identified IgMs and recombinant Ig fragments that hydrolyze Abeta. Hydrolysis of peripheral Abeta by the IgMs may induce increased Abeta release from the brain. The catalytic IgMs are increased in AD patients, presumably reflecting a protective autoimmune response. Reduced Abeta aggregation...
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PMID: 18486927
PDF is available here.
Abstract
The competing reaction pathways and the corresponding free energy barriers for cocaine hydrolysis catalyzed by an anti-cocaine catalytic antibody, mAb15A10, were studied by using a novel computational strategy based on the binding free energy calculations on the antibody binding with cocaine and tran...
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PMID: 18341277
PDF is available here.
Abstract
(-)-Cocaine is a widely abused drug and there is currently no available anti-cocaine therapeutic. Promising agents, such as anti-cocaine catalytic antibodies and high-activity mutants of human butyrylcholinesterase (BChE), for therapeutic treatment of cocaine overdose have been developed through stru...
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PMID: 18292872
PDF is available here.
Alexey A AA Belogurov,
Inna N IN Kurkova,
Alain A Friboulet,
Daniel D Thomas,
Viktor K VK Misikov,
Maria Yu MY Zakharova,
Sergey V SV Suchkov,
Sergey V SV Kotov,
Alexander I AI Alehin,
Bérangère B Avalle,
Ekaterina A EA Souslova,
Herbert C HC Morse,
Alexander G AG Gabibov and
Natalia A NA Ponomarenko
Abstract
We reported that anti-myelin basic protein (MBP) serum Abs from multiple sclerosis (MS) patients exhibit proteolytic activity toward the autoantigen. The aim of this study is to determine MBP epitopes specific for the autoantibodies in MS and compare these data with those from other neuronal disorde...
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PMID: 18178866
PDF is available here.
Abstract
We have successfully developed a catalytic antibody capable of degrading the active site of the urease of Helicobacter pylori and eradicating the bacterial infection in a mouse stomach. This monoclonal antibody UA15 was generated using a designed recombinant protein UreB, which contained the crucial...
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PMID: 17991752
PDF is available here.
Abstract
The Diels-Alder reaction is one of the most important and versatile transformations available to organic chemists for the construction of complex natural products, therapeutics agents, and synthetic materials. Given the lack of efficient enzymes capable of catalyzing this kind of reaction, it is of...
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PMID: 17960540
PDF is available here.
Abstract
We show that immunization of healthy rabbits with bovine DNase I produces IgGs with intrinsic DNase and RNase activities. Electrophoretically and immunologically homogeneous polyclonal IgGs were obtained by sequential chromatography of the immune sera on Protein A-Sepharose and gel filtration. Affin...
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PMID: 18446884
PDF is available here.
Abstract
Catalytic activity of certain antibodies was proposed by Linus Pauling for the very first time more than six decades ago. Since then few examples of catalytic antibodies (abzymes) were found in human organism. From late 80's many synthetic abzymes were obtained after immunization by Transition State...
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PMID: 18673227
PDF is available here.
Abstract
We developed an electrochemical surface plasmon resonance flow cell for the simultaneous measurement of the binding affinity and catalytic activity of bifunctional biomolecules. These measurements will be useful for evaluating the performance of such biomolecules as ribozyme and abzyme. The simultan...
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PMID: 17973351
PDF is available here.
Stephanie S Planque,
Yukie Y Mitsuda,
Hiroaki H Taguchi,
Maria M Salas,
Mary-Kate MK Morris,
Yasuhiro Y Nishiyama,
Robert R Kyle,
Pablo P Okhuysen,
Miguel M Escobar,
Robert R Hunter,
Haynes W HW Sheppard,
Carl C Hanson and
Sudhir S Paul
Abstract
Antibody hydrolysis of the superantigenic gp120 site and HIV-1 neutralization was studied as a potential anti-HIV mechanism in uninfected humans. gp120 hydrolysis by purified serum and salivary antibodies was determined by electrophoresis and peptide sequencing, the proteolytic mechanism was analyze...
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PMID: 18160012
PDF is available here.
Abstract
These results suggest the possibility of new approach for the creation of tailor-made proteases beyond limitations of the traditional immunization approach....
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PMID: 17899065
PDF is available here.
Abstract
We compared the catAb with the non-catalytic antibody (non-catAb) for interaction with the non-cleavable amide substrate (a mimic of the ester substrate) and the two end products. Surface plasmon resonance (SPR) analysis revealed that the amide substrate gave the equivalent K(d) values for the two a...
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PMID: 17981825
PDF is available here.
Abstract
Antibodies with enzymatic activity were named abzymes or catalytic antibodies. In the present study, the lipolytic abzymes were selected from the phage displayed antibody libraries against a transition state analog (TSA) of lipases/esterases. After three rounds of selection, four monoclonal phage pa...
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PMID: 17673171
PDF is available here.
Abstract
We review strategies to alter mosquito vector competence and consider issues related to translating this knowledge to field applications....
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PMID: 17877001
PDF is available here.
Abstract
We studied polyclonal IgA and IgG preparations from healthy human sera and saliva for the ability to hydrolyze model peptidyl-aminomethylcoumarin (peptide-AMC) substrates. These substrates permit objective evaluation of the catalytic potential of the antibody classes with minimal effects of noncoval...
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PMID: 17914190
PDF is available here.
Abstract
Catalytic antibodies 6D9 and 9C10, which were induced by immunization with a haptenic transition-state analog (TSA), catalyze the hydrolysis of a nonbioactive chloramphenicol monoester derivative to generate a bioactive chloramphenicol. These antibodies stabilize the transition state to catalyze the...
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PMID: 17428500
PDF is available here.
Abstract
We performed an extensive proteomic investigation on plasma of type 1 diabetic subjects to discover why some of them apparently lacked any measurable proteolytic activity. Activity was found enclosed in immune complexes in which Fab/(Fab)(2) displayed a serine-like catalytic activity. Disaggregation...
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PMID: 17298847
PDF is available here.
Abstract
Phosphorylation plays an important role in regulation of living functions of organisms; phosphorylation may significantly alter chemical properties of proteins, lipids, and carbohydrates. Canonical kinases catalyze transfer of terminal phosphate group from ATP (or other NTPs) to specific nucleophili...
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PMID: 17511601
PDF is available here.
Abstract
We report the generation of catalytic Abs that effectively target tumor cells with undiminished prodrug activation capability. Ab conjugates were prepared by covalent conjugation of an integrin alpha(v)beta(3)-targeting antagonist to catalytic Ab 38C2 through either sulfide groups of cysteine residu...
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PMID: 17372220
PDF is available here.
Abstract
We performed NMR analysis of the Fv fragment of 6D9 (6D9-Fv), together with site-directed mutagenesis and stopped-flow kinetic analyses. Among six 6D9-Fv mutants, Y58(H)A and W100i(H)A displayed significant reductions in their affinities to the TSA, while their substrate-binding affinities were iden...
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PMID: 17239396
PDF is available here.
Abstract
We report the generation and characterization of a monoclonal antibody, YX1-40H10, that catalyzes the photooxidation of (+)-2 into the nonpsychoactive compound benzaldehyde (14) under anaerobic conditions in the presence of riboflavin (6). Studies have revealed that the antibody facilitates the conv...
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PMID: 17360412
PDF is available here.
Abstract
We have developed a new assay to allow direct visualization of retro-aldol retro-Michael catalytic activity and have demonstrated it with catalytic antibody 38C2. The assay is based on a catalytic cleavage of a physiologically stable substrate to release 3,4-cyclohexeneoesculetin. The latter then re...
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PMID: 17234408
PDF is available here.
Abstract
A kinetically homogeneous anti-phosphate catalytic antibody preparation was shown to catalyse the hydrolysis of a series of O-aryl N-methyl carbamates containing various substituents in the 4-position of the O-phenyl group. The specific nature of the antibody catalysis was demonstrated by the adhere...
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PMID: 17020536
PDF is available here.
Abstract
These results indicate the power of initial selection of catalytic antibodies from a biased antibody library in both rapid generation and screening of mutants for improved catalysis....
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PMID: 17084858
PDF is available here.
Abstract
Natural antibodies possessing catalytic activity present a new group of biologically active substances that are found in various autoimmune diseases such as autoimmune thyroiditis, myocarditis, multiple sclerosis, and system lupus erythematosus. Presently, an interconnection between the activity of...
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PMID: 17722295
PDF is available here.
Abstract
We present data that such sIgA-abzymes, purified by sequential chromatography on DEAE-fractogel, heparin-sepharose, DNA-cellulose and followed by gel-filtration, are also able to hydrolyse total RNA from E. coli better than plasmid DNA. Besides, such sIgA-abzymes effectively cleaved 18S and 28S ribo...
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PMID: 17988015
PDF is available here.
Abstract
The review is focused on the analysis of published data and the results obtained by the authors about the catalytic activity of antibodies (abzymes) of human colostrum and milk. Possible mechanisms of origination of these abzymes and their potential role in the regulation of biological activity of h...
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PMID: 18030744
PDF is available here.
Abstract
We study on directed evolution with antibody libraries. We have succeeded in generating highly active catalytic antibodies in phage-displayed antibody (Fab) libraries. To evolve catalytic antibodies toward higher catalytic activity, we have mimicked an enzyme-evolutional process, in which an enzyme...
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PMID: 17202788
PDF is available here.
Abstract
These results suggest that acetylcholinesterase activity may be inherent to cocaine esterases....
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PMID: 17131989
PDF is available here.
Abstract
We performed a series of site-directed mutagenesis experiments of catalytic antibody, 6D9, which hydrolyzes a prodrug of chloramphenicol, based on our previous directed evolution study [Takahashi et al. (2001) Nat. Biotechnol. 19, 563-567]. Since we previously found that the variants with a mutation...
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PMID: 16921165
PDF is available here.
Abstract
Antibodies that catalyze the deprotonation of unactivated benzisoxazoles to give the corresponding salicylonitriles were prepared using as antigen a 2-aminobenzimidazolium derivative coupled to a carrier protein via its benzene ring. The hapten was designed to induce an antibody binding site with bo...
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PMID: 16782349
PDF is available here.
Abstract
Antibody 15A9, raised with 5'-phosphopyridoxyl (PPL)-N(epsilon)-acetyl-L-lysine as hapten, catalyzes the reversible transamination of hydrophobic D-amino acids with pyridoxal 5'-phosphate (PLP). The crystal structures of the complexes of Fab 15A9 with PPL-L-alanine, PPL-D-alanine, and the hapten wer...
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PMID: 16790434
PDF is available here.
Abstract
We report for the first time, production of monoclonal antibody (MAb) against beta human chorionic gonadotropin (hCG) with proteolytic activity. MAb "7D9" was raised in Balb/C mice using purified human chorionic gonadotropin. Immunoblot analysis and enzyme-linked immunoabsorbent assay (ELISA) showed...
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PMID: 16759712
PDF is available here.
Sébastien S Lacroix-Desmazes,
Bharath B Wootla,
Suryasarathi S Dasgupta,
Sandrine S Delignat,
Jagadeesh J Bayry,
Joseph J Reinbolt,
Johan J Hoebeke,
Evgueni E Saenko,
Michel D MD Kazatchkine,
Alain A Friboulet,
Olivier O Christophe,
Valakunja V Nagaraja and
Srini V SV Kaveri
Abstract
We have shown previously that a subset of anti-factor VIII IgG hydrolyzes FVIII. FVIII-hydrolyzing IgG are detected in over 50% of inhibitor-positive patients with severe hemophilia A, and are not found in inhibitor-negative patients. Although human proficient catalytic Abs have been described in a...
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PMID: 16818797
PDF is available here.
Abstract
We propose that catalytic antibodies have either a beneficial or a deleterious role depending on the physiopathological context. Physiology thus relies on a delicate equilibrium between the levels of soluble target antigen and that of antigen-specific hydrolyzing immunoglobulins. Indeed, in patients...
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PMID: 16651863
PDF is available here.
Abstract
We tested the effects of seven BJPs on LLC-PK1 cells to assess their pathogenicity. Two out of the seven BJPs showed cytotoxic activity, as assessed by microscopic analysis, the WST method and TUNEL staining. Moreover, the cytotoxic BJPs were excreted by patients who presented with renal impairment....
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PMID: 16740125
PDF is available here.
Abstract
H11 is the first antibody reported to have dual activity as a non-concerted, Diels-Alderase and hydrolytic catalyst. It was previously shown to catalyse the cycloaddition of acetoxybutadiene 1a to N-alkyl maleimides 2 to afford hydroxy-substituted bicyclic adducts 3 with a 30% ee of a major isomer....
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PMID: 16378728
PDF is available here.
Abstract
Antibodies (Abs) with proteolytic and other catalytic activities have been characterized in the blood and mucosal secretions of humans and experimental animals. The catalytic activity can be traced to nucleophilic sites of innate origin located in Ab germline variable regions. Discoveries of the nat...
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PMID: 16290203
PDF is available here.
Abstract
We present the results of new functional analysis of the anti-MBP autoantibodies isolated from MS (in patients) and EAE (in mice) sera, based on their proteolytic activity against the targeted autoantigen. The activity was shown to be the intrinsic property of the IgG molecule. No activity was found...
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PMID: 16297986
PDF is available here.
Abstract
These results support a designer strategy for generating nucleophilic abzymes and could also account for the occurrence of chemically reactive or catalytic antibodies in natural immunity or autoimmunity....
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PMID: 16297987
PDF is available here.