Catalytic Antibodies: Design, Expression, and Their Applications in Medicine

Zhao, Daqun; Chen, Jie; Hu, Xiaoyue; Zhang, Shujun

doi:10.1007/s12010-022-04183-1

Cited by 8 publications

(7 citation statements)

References 186 publications

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“…Various antibodies with catalytic activities—abzymes (Abzs) against chemically stable analogs of transition states of some chemical reactions catalyzing more than 190 various reactions—are obtained as novel important enzymes (for review, see [ 1 , 2 , 3 , 4 , 5 , 6 ]). Natural catalytic auto-Abz splitting polysaccharides, nucleic acids, nucleotides, different oligopeptides, and proteins were detected in the blood of patients with many autoimmune diseases (AIDs) (for review, see [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]).…”

Section: Introductionmentioning

confidence: 99%

“…Despite their classification into over one hundred families, all phosphatases still catalyze the same general hydrolysis reaction [ 49 , 50 ]. Artificial Abzs against stable analogues of transition states of different chemical reactions are described [ 1 , 2 , 3 , 4 , 5 , 6 ]. Like artificial Abzs, natural abzymes are Abs against enzyme substrates acting as protein haptens, mimicking transition states of chemical reactions.…”

Section: Introductionmentioning

confidence: 99%

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Autoantibodies-Abzymes with Phosphatase Activity in Experimental Autoimmune Encephalomyelitis Mice

Urusov,

Aulova,

Nevinsky

2024

Molecules

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The exact mechanisms of MS (multiple sclerosis) evolution are still unknown. However, the development of EAE (experimental autoimmune encephalomyelitis simulating human MS) in C57BL/6 mice occurs due to the violation of bone marrow hematopoietic stem cell differentiation profiles, leading to the production of toxic for human autoantibody splitting MBP (myelin basic protein), MOG (mouse oligodendrocyte glycoprotein), five histones, DNA, and RNA. Here, we first analyzed the changes in the relative phosphatase activity of IgGs from C57BL/6 mice blood over time, corresponding to three stages of EAE: onset, acute, and remission. Antibodies have been shown to catalyze the hydrolysis of p-nitrophenyl phosphate at several optimal pH values, mainly in the range of 6.5–7.0 and 8.5–9.5. During the spontaneous development of EAE, the most optimal value is pH 6.5. At 50 days after the birth of mice, the phosphatase activity of IgGs at pH 8.8 is 1.6-fold higher than at pH 6.5. During spontaneous development of EAE from 50 to 100 days, an increase in phosphatase activity is observed at pH 6.5 but a decrease at pH 8.8. After mice were immunized with DNA–histone complex by 20 and 60 days, phosphatase activity increased respectively by 65.3 and 109.5 fold (pH 6.5) and 128.4 and 233.6 fold (pH 8.8). Treatment of mice with MOG at the acute phase of EAE development (20 days) leads to a maximal increase in the phosphatase activity of 117.6 fold (pH 6.5) and 494.7 fold (pH 8.8). The acceleration of EAE development after mice treatment with MOG and DNA–histone complex results in increased production of lymphocytes synthesizing antibodies with phosphatase activity. All data show that IgG phosphatase activity could be essential in EAE pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autoantibodies-Abzymes with Phosphatase Activity in Experimental Autoimmune Encephalomyelitis Mice

Urusov,

Aulova,

Nevinsky

2024

Molecules

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“…The primary physiological function of antibodies is to recognize and eliminate the antigen. However, antibodies are also capable of catalyzing specific chemical reactions [ 13 , 14 , 15 ]. Natural catalytic antibodies have been found in a variety of physiological and pathological conditions, including viral infections and autoimmune diseases [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2

Timofeeva,

Sedykh,

Sedykh

et al. 2023

Vaccines

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The S-protein is the major antigen of the SARS-CoV-2 virus, against which protective antibodies are generated. The S-protein gene was used in adenoviral vectors and mRNA vaccines against COVID-19. While the primary function of antibodies is to bind to antigens, catalytic antibodies can hydrolyze various substrates, including nucleic acids, proteins, oligopeptides, polysaccharides, and some other molecules. In this study, antibody fractions with affinity for RBD and S-protein (RBD-IgG and S-IgG) were isolated from the blood of COVID-19 patients vaccinated with Sputnik V. The fractions were analyzed for their potential to hydrolyze 18-mer oligopeptides corresponding to linear fragments of the SARS-CoV-2 S-protein. Here, we show that the IgG antibodies hydrolyze six out of nine oligopeptides efficiently, with the antibodies of COVID-19-exposed donors demonstrating the most significant activity. The IgGs of control donors not exposed to SARS-CoV-2 were found to be inactive in oligopeptide hydrolysis. The antibodies of convalescents and vaccinated patients were found to hydrolyze oligopeptides in a wide pH range, with the optimal pH range between 6.5 and 7.5. The hydrolysis of most oligopeptides by RBD-IgG antibodies is inhibited by thiol protease inhibitors, whereas S-IgG active centers generally combine several types of proteolytic activities. Ca2+ ions increase the catalytic activity of IgG preparations containing metalloprotease-like active centers. Thus, the proteolytic activity of natural antibodies against the SARS-CoV-2 protein is believed to be due to the similarity of catalytic antibodies’ active centers to canonical proteases. This work raises the question of the possible physiological role of proteolytic natural RBD-IgG and S-IgG resulting from vaccination and exposure to COVID-19.

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“…Natural antibodies exhibit lower affinity and cross-reactivity compared to antigen-specific antibodies [26]. Among natural antibodies, IgGs with catalytic properties called abzymes, are also known [27][28][29]. Interestingly, catalytic antibodies that recognize and hydrolyze DNA were first discovered in SLE patients [30].…”

Section: Introductionmentioning

confidence: 99%

“…Monoclonal catalytic antibodies exhibiting DNase activity were also obtained [31,32]. Data on the catalytic activity of DNAhydrolyzing abzymes in SLE, multiple sclerosis, and several other autoimmune and viral diseases have been summarized in several reviews [27][28][29]33,34]. However, the sequence specificity of anti-DNA IgG with catalytic activity in SLE has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Hydrolysis of Oligodeoxyribonucleotides on the Microarray Surface and in Solution by Catalytic Anti-DNA Antibodies in Systemic Lupus Erythematosus

Novikova,

Ermakov,

Kostina

et al. 2023

CIMB

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Anti-DNA antibodies are known to be classical serological hallmarks of systemic lupus erythematosus (SLE). In addition to high-affinity antibodies, the autoantibody pool also contains natural catalytic anti-DNA antibodies that recognize and hydrolyze DNA. However, the specificity of such antibodies is uncertain. In addition, DNA binding to a surface such as the cell membrane, can also affect its recognition by antibodies. Here, we analyzed the hydrolysis of short oligodeoxyribonucleotides (ODNs) immobilized on the microarray surface and in solution by catalytic anti-DNA antibodies from SLE patients. It has been shown that IgG antibodies from SLE patients hydrolyze ODNs more effectively both in solution and on the surface, compared to IgG from healthy individuals. The data obtained indicate a more efficient hydrolysis of ODNs in solution than immobilized ODNs on the surface. In addition, differences in the specificity of recognition and hydrolysis of certain ODNs by anti-DNA antibodies were revealed, indicating the formation of autoantibodies to specific DNA motifs in SLE. The data obtained expand our understanding of the role of anti-DNA antibodies in SLE. Differences in the recognition and hydrolysis of surface-tethered and dissolved ODNs need to be considered in DNA microarray applications.

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Catalytic Antibodies: Design, Expression, and Their Applications in Medicine

Cited by 8 publications

References 186 publications

Autoantibodies-Abzymes with Phosphatase Activity in Experimental Autoimmune Encephalomyelitis Mice

Autoantibodies-Abzymes with Phosphatase Activity in Experimental Autoimmune Encephalomyelitis Mice

Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2

Hydrolysis of Oligodeoxyribonucleotides on the Microarray Surface and in Solution by Catalytic Anti-DNA Antibodies in Systemic Lupus Erythematosus

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