Hubbry Logo
AbzymeAbzymeMain
Open search
Abzyme
Community hub
Abzyme
logo
7 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Abzyme
Abzyme
Abzyme
View on Wikipedia
from Wikipedia

An abzyme[1] (from antibody and enzyme), also called catmab (from catalytic monoclonal antibody),[2] and most often called catalytic antibody or sometimes catab,[3] is a monoclonal antibody with catalytic activity. Abzymes are usually raised in lab animals immunized against synthetic haptens, but some natural abzymes can be found in normal humans (anti-vasoactive intestinal peptide autoantibodies) and in patients with autoimmune diseases such as systemic lupus erythematosus, where they can bind to and hydrolyze DNA.[1] To date abzymes display only weak, modest catalytic activity and have not proved to be of any practical use.[4] They are, however, subjects of considerable academic interest. Studying them has yielded important insights into reaction mechanisms, enzyme structure and function, catalysis, and the immune system itself.[4]

Enzymes function by lowering the activation energy of the transition state of a chemical reaction, thereby enabling the formation of an otherwise less-favorable molecular intermediate between the reactant(s) and the product(s). If an antibody is developed to bind to a molecule that is structurally and electronically similar to the transition state of a given chemical reaction, the developed antibody will bind to, and stabilize, the transition state, just like a natural enzyme, lowering the activation energy of the reaction, and thus catalyzing the reaction. By raising an antibody to bind to a stable transition-state analog, a new and unique type of enzyme is produced.

So far, all catalytic antibodies produced have displayed only modest, weak catalytic activity. The reasons for low catalytic activity for these molecules have been widely discussed. Possibilities indicate that factors beyond the binding site may play an important role, in particular through protein dynamics.[5] Some abzymes have been engineered to use metal ions and other cofactors to improve their catalytic activity.[6][7]

History

[edit]

The possibility of catalyzing a reaction by means of an antibody which binds the transition state was first suggested by William P. Jencks in 1969.[8] In 1994 Peter G. Schultz and Richard A. Lerner received the prestigious Wolf Prize in Chemistry for developing catalytic antibodies for many reactions and popularizing their study into a significant sub-field of enzymology.[9]

Abzymes in healthy human breast milk

[edit]

There are a broad range of abzymes in healthy human breast milk with DNAse, RNAse, and protease activity.[4]

Potential HIV treatment

[edit]

In a June 2008 issue of the journal Autoimmunity Review,[10][11] researchers S. Planque, Sudhir Paul, Ph.D., and Yasuhiro Nishiyama, Ph.D. of the University Of Texas Medical School at Houston announced that they have engineered an abzyme that degrades the superantigenic region of the gp120 CD4 binding site. This is the one part of the HIV virus outer coating that does not change, because it is the attachment point to T lymphocytes, the key cell in cell-mediated immunity. Once infected by HIV, patients produce antibodies to the more changeable parts of the viral coat. The antibodies are ineffective because of the virus' ability to change their coats rapidly. Because this protein gp120 is necessary for HIV to attach, it does not change across different strains and is a point of vulnerability across the entire range of the HIV variant population.

The abzyme does more than bind to the site: it catalytically destroys the site, rendering the virus inert, and then can attack other HIV viruses. A single abzyme molecule can destroy thousands of HIV viruses.

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Abzyme

View on Grokipedia
from Grokipedia
An abzyme, short for or catalytic , is a engineered or naturally occurring that possesses enzymatic activity, enabling it to bind to specific antigens while simultaneously catalyzing chemical reactions such as , much like traditional enzymes. These molecules mimic the active sites of enzymes by stabilizing transition states, thereby lowering and accelerating reactions with high specificity and . The concept of catalytic antibodies originated from transition state theory, first proposed by William Jencks in 1969, who suggested that antibodies raised against transition state analogs could exhibit enzyme-like properties. This idea was experimentally realized in 1986 through independent work by Richard Lerner's group at the Scripps Research Institute and others, who generated the first artificial abzymes capable of hydrolyzing esters and carbonates by immunizing mice with hapten mimics of reaction transition states. Natural abzymes were discovered shortly thereafter in 1989 by Sudhir Paul and colleagues, who identified catalytic immunoglobulins in human serum that hydrolyzed vasoactive intestinal peptide, often associated with autoimmune conditions like systemic lupus erythematosus (SLE). Abzymes are generated artificially through immunization with synthetic haptens designed to resemble unstable transition states, followed by hybridoma technology to produce monoclonal antibodies, or via modern recombinant methods such as phage display and directed evolution to enhance catalytic efficiency. In contrast, natural abzymes arise endogenously, typically in patients with autoimmune diseases, where dysregulated immune responses lead to antibodies that inadvertently catalyze self-tissue damage, such as DNA or myelin basic protein hydrolysis in SLE or multiple sclerosis. While abzymes generally exhibit lower catalytic rates (k_cat) than natural enzymes—often by orders of magnitude—they offer advantages like exceptional substrate specificity, thermal stability, and extended half-lives in vivo, making them promising for therapeutic applications. Notable advances in abzyme research include their use in prodrug activation for targeted cancer therapy, exemplified by the aldolase antibody 38C2, which converts inert prodrugs into active cytotoxins at tumor sites. They have also shown potential in treating substance addiction by hydrolyzing cocaine or heroin, and in neurodegenerative diseases by degrading amyloid-beta plaques in Alzheimer's models, as demonstrated with abzyme 2E6. Additionally, antiviral abzymes like 3D8 have been explored for cleaving viral glycoproteins, including those of SARS-CoV-2, highlighting their evolving role in infectious disease management. Recent studies as of 2025 have identified natural abzyme-like proteolytic activities in antibodies from COVID-19 convalescent patients, potentially contributing to viral clearance. Despite challenges such as immunogenicity and optimization of catalytic proficiency, ongoing genetic engineering efforts continue to expand their biomedical utility.

Fundamentals

Definition and Characteristics

Abzymes, also known as catalytic antibodies, are immunoglobulins that exhibit both antigen-binding specificity and enzymatic catalytic activity, enabling them to accelerate chemical reactions by mimicking the function of natural enzymes. These molecules represent a hybrid of immune recognition and , where the antibody's variable region serves as an tailored to particular substrates. Key characteristics of abzymes include their ability to combine the precise substrate specificity derived from antibody-antigen interactions with catalytic turnover, allowing multiple reaction cycles per antibody molecule. Unlike conventional antibodies, which are immune proteins that bind antigens without promoting chemical change, abzymes lower the of reactions by binding more tightly to the than to the of the substrate, thereby facilitating rate enhancements comparable to some enzymes. This dual functionality positions abzymes as versatile biocatalysts with potential for targeted applications. Abzymes catalyze a range of , including the of esters, amides, and , where they accelerate bond cleavage in these substrates through transition-state stabilization. For example, specific abzymes have been developed to hydrolyze carbonate esters at rates enhanced by orders of magnitude relative to uncatalyzed . Abzymes are generated by immunizing host organisms with transition-state analogs—stable molecular mimics of the reaction's high-energy intermediate—rather than haptens that directly represent the substrate's . This immunization strategy elicits antibodies whose binding pockets are pre-shaped to stabilize the , distinguishing abzymes from standard antigen-binding antibodies and enabling their catalytic prowess.

Comparison to Antibodies and Enzymes

Abzymes, or catalytic antibodies, differ from traditional antibodies primarily in their ability to not only bind antigens but also catalyze chemical reactions involving those antigens. Conventional antibodies facilitate non-covalent binding to specific epitopes without subsequent turnover, effectively sequestering targets but lacking enzymatic reactivity. In contrast, abzymes incorporate catalytic functionality, enabling them to cleave or modify bound substrates, such as through of esters or peptides, while maintaining the high specificity of antibody-antigen interactions. Compared to natural enzymes, abzymes exhibit lower catalytic efficiency due to their unevolved active sites, which are shaped by immune responses rather than millions of years of optimization. s can achieve k_cat/K_m values up to 10^8 to 10^9 M^{-1} s^{-1} near the diffusion limit, though median values are around 10^5 M^{-1} s^{-1}. Abzymes, however, generally display k_cat/K_m values of 10^2 to 10^4 M^{-1} s^{-1}, as their binding pockets prioritize transition-state stabilization over the precise geometry of dedicated enzyme active sites. This hybrid nature confers unique advantages, combining the exquisite specificity of antibodies for rare or disease-specific antigens with enzyme-like reactivity to enable targeted degradation or modification. For instance, abzymes can selectively hydrolyze pathological proteins, such as amyloid-beta in models, offering potential for therapies that minimize off-target effects. Quantitatively, abzymes provide rate enhancements of 10^3 to 10^6-fold relative to uncatalyzed reactions, sufficient for therapeutic applications despite falling short of natural accelerations, which can exceed 10^{12}-fold.

Discovery and Development

Initial Discovery

The concept of catalytic antibodies, or abzymes, traces its theoretical origins to biochemist William P. Jencks, who in 1969 proposed that antibodies elicited against stable mimics of a reaction's could stabilize that state and thereby catalyze the reaction, drawing from Linus Pauling's transition-state theory. This idea suggested exploiting the immune system's ability to generate high-affinity binding sites to mimic enzyme active sites, though it remained untested for nearly two decades. The initial experimental realization of abzymes occurred in 1986, when Richard A. Lerner and colleagues at the Scripps Research Institute in , , successfully generated monoclonal antibodies capable of catalyzing chemical reactions. Their approach involved designing a —a analog of the tetrahedral for carbonate ester —and conjugating it to a carrier protein like to make it immunogenic. Mice were immunized with this conjugate, and spleen cells were fused with myeloma cells using to produce monoclonal antibodies, which were then screened for catalytic activity against the corresponding ester substrate. One such antibody demonstrated rate accelerations of up to 10,000-fold for the of p-nitrophenyl carbonate, confirming the feasibility of inducing catalytic sites through immunization with transition-state mimics. Independently, in the same year, Peter G. Schultz's group at the , reported the parallel discovery of abzymes using a similar strategy. They immunized mice with a diester mimicking the for carboxylic and isolated monoclonal antibodies that selectively catalyzed the of a fluorodinitrophenyl with specificity comparable to natural enzymes. These foundational experiments, both published in Science on December 19, 1986, marked the birth of abzyme research by validating Jencks' hypothesis and opening the door to tailored biocatalysts.

Key Research Milestones

In 1989, the discovery of the first natural catalytic antibody, or abzyme, marked a significant advancement beyond artificial constructs, as Sudhir Paul and colleagues identified an from human serum capable of hydrolyzing (VIP) at a specific calpain cleavage site, demonstrating intrinsic catalytic potential without prior . This finding expanded the scope of abzyme research to include endogenous antibodies, suggesting evolutionary roles in physiological processes. During the 1990s, progress accelerated with the engineering of abzymes for complex synthetic reactions, showcasing their versatility as programmable catalysts. Research groups, including those led by Richard Lerner and Kim Janda at Scripps Research Institute, developed catalytic antibodies that facilitated Diels-Alder cycloadditions, with notable examples controlling endo versus exo to achieve high enantiomeric excess in bimolecular reactions. Concurrently, aldolase abzymes emerged as efficient mediators of carbon-carbon bond formation; the 38C2, elicited against a β-diketone , catalyzed retro-aldol and aldol condensations via an mechanism, mimicking natural class I aldolases with k_cat values up to 0.023 s⁻¹ and modest rate accelerations. These developments highlighted abzymes' potential in asymmetric synthesis, though catalytic efficiencies remained orders of magnitude below natural enzymes. The 2000s saw the integration of for of abzymes, enabling iterative optimization of catalytic properties. Pioneering work by the Janda group utilized libraries to evolve variants of an esterolytic abzyme, achieving up to 100-fold improvements in k_cat/K_M through affinity maturation toward transition-state analogs, as demonstrated in selections for of p-nitrophenyl . This approach addressed limitations in traditional by allowing and , fostering abzymes with enhanced substrate specificity and turnover rates suitable for biotechnological applications. In the , investigations into natural abzymes gained momentum, particularly in autoimmune contexts, revealing their association with disease pathology. Studies on systemic lupus erythematosus (SLE) patients identified polyclonal IgG abzymes with DNA-hydrolyzing activity, often exceeding that in healthy controls by 10- to 50-fold in relative activity units, linked to B-cell dysregulation and potential roles in nucleolytic damage. These findings, corroborated across cohorts, underscored abzymes as biomarkers for autoimmune progression while prompting explorations into their immunomodulatory functions. In the 2020s, abzyme research has advanced toward therapeutic applications, particularly in infectious diseases. For instance, the single-chain variable fragment 3D8, a nucleic acid-hydrolyzing catalytic antibody, was demonstrated to inhibit the replication of and other coronaviruses in cell cultures by targeting viral nucleic acids.

Scientific Basis

Mechanism of Catalysis

Abzymes facilitate catalysis primarily through the stabilization of s within the antibody binding pocket, a concept rooted in Jencks' , which posits that catalysts lower by binding more tightly to the high-energy than to the ground-state substrate. This selective stabilization distorts the substrate toward the geometry, accelerating the reaction rate by factors of 10^2 to 10^6 compared to the uncatalyzed process. The begins with substrate binding to the complementarity-determining regions of the , where the binding pocket is designed via with transition-state analogs to mimic the reaction's fleeting intermediate. This mimicry induces strain or desolvation in the bound substrate, promoting progression to the ; catalysis then proceeds, followed by product release, though high-affinity interactions can limit turnover numbers to below 10 min^{-1} in many cases. In hydrolysis reactions, a common catalytic mode for abzymes, the mechanism often involves nucleophilic attack on the substrate's electrophilic center, such as a carbonyl group, facilitated by activated water or a residue like serine acting as the nucleophile. Some abzymes emulate serine protease mechanisms through a Ser-His dyad that deprotonates the nucleophile, enabling efficient bond cleavage while stabilizing the oxyanion intermediate. Catalytic efficiency in abzymes is further bolstered by electrostatic preorganization in the , where polar and charged residues are optimally aligned to solvate and stabilize transition-state charges without the energetic penalty of dielectric reorganization seen in solution. This prearranged electrostatic environment contributes up to 10^5-fold rate enhancements by minimizing desolvation costs during substrate binding.

Structural Features

Abzymes, or catalytic antibodies, derive their catalytic capability from the variable regions of their immunoglobulin structure, specifically the variable heavy (VH) and variable light (VL) domains, which together form the antigen-binding site adapted for enzymatic function. These domains are located at the N-terminal ends of the heavy and light chains, respectively, and their juxtaposition creates a that can stabilize transition states of substrates, mimicking active sites. The catalytic site is predominantly shaped by the six complementarity-determining regions (CDRs)—three from VH (CDRH1–3) and three from VL (CDRL1–3)—which exhibit hypervariability to accommodate diverse substrates. Key structural motifs in abzymes include deep pockets formed by the flexible CDR loops, particularly CDRH3, which can extend to create enclosed cavities for substrate binding and catalysis. Within these pockets, charged residues such as (Asp) and (His) play pivotal roles in acid-base catalysis; for instance, Asp residues often position substrates for nucleophilic attack, while His facilitates proton transfer, as seen in engineered abzymes with Asp-His dyads in the VL domain. Examples include the introduction of Asp1, His93, and Ser27a in specific CDRs to form triad-like arrangements that enhance hydrolytic activity. Compared to natural enzymes, abzymes lack the evolutionary refinement that optimizes pocket geometry and residue positioning, resulting in broader substrate specificity but lower catalytic fidelity and efficiency, such as reduced rate accelerations. This structural plasticity, however, allows abzymes to catalyze reactions without pre-existing enzymatic templates, enabling the design of novel catalysts. To improve catalytic performance, engineering approaches like target CDR residues to introduce or reposition key catalytic , such as replacing non-functional residues with His or Asp to boost activity by orders of magnitude in model abzymes. For example, in the VH domain of an anti-hapten has been used to incorporate acid-base pairs, thereby enabling the structure to better stabilize transition states.

Natural Occurrence and Applications

Presence in Human Biology

Abzymes, or catalytic antibodies, occur naturally in human biology at low levels in the serum of healthy individuals. These natural abzymes are present in various physiological fluids, including serum and mucosal secretions, where they exhibit enzymatic activities without association to disease states. In healthy human , both IgG and secretory IgA (sIgA) immunoglobulins demonstrate abzyme activity, particularly in hydrolyzing nucleic acids and proteins. Studies from the identified that the light chains of IgG antibodies in possess DNA-hydrolyzing (DNase) activity, enabling the cleavage of DNA substrates. Additionally, sIgA abzymes in hydrolyze myelin basic protein (MBP), a key component of the myelin sheath, as well as histones, suggesting a role in processing specific biomolecules in this protective fluid. These findings indicate that milk-derived abzymes may contribute to the and regulatory properties of . Natural abzymes may play a role in immune regulation within healthy , potentially aiding in the clearance of apoptotic cells and the neutralization of pathogens through their catalytic functions. This involvement helps maintain by facilitating the breakdown of cellular debris and microbial components. From an evolutionary perspective, abzymes represent a primitive catalytic capability in the , providing insights into the development of multifunctional immunoglobulins that bridge binding and enzymatic roles in early adaptive responses.

Therapeutic Potential

Abzymes hold significant promise in therapeutic applications due to their ability to combine the specificity of antibodies with catalytic activity, enabling targeted degradation of harmful molecules . This dual functionality allows for precise interventions in diseases involving specific substrates, such as viral proteins or toxic compounds, potentially minimizing systemic side effects compared to traditional small-molecule drugs. In the context of HIV treatment, abzymes have been developed to target the gp120, which is essential for viral attachment to host + cells. Early research in the identified catalytic antibodies, such as IgA and IgG variants, that proteolytically cleave gp120 at conserved sites like residues 421–433, disrupting its structure and neutralizing viral infectivity and in animal models. These abzymes demonstrated potent inhibition of -1 strains, including B and C variants, but their was limited by the virus's high , which can alter epitopes and reduce catalytic targeting over time. No clinical trials have advanced beyond preclinical stages, though their potential as passive immunotherapies or microbicides persists. For cocaine detoxification, abzymes like 15A10 catalyze the of 's benzoyl ester, converting it into non-psychoactive metabolites such as and ecgonine methyl ester. Preclinical studies in showed that 15A10 effectively blocks 's reinforcing effects, cardiovascular , and lethality by rapidly clearing the drug from circulation, with doses as low as 10 mg/kg achieving complete attenuation in behavioral models. This approach remains in , with no reported Phase I trials for catalytic abzymes specifically, though related anti- technologies entered early clinical testing in the . In cancer therapy, abzymes offer potential through mechanisms like antibody-directed abzyme prodrug therapy (ADAPT), where catalytic antibodies such as 38C2 or EA11-D7 activate inert s at tumor sites to release cytotoxic agents. For instance, 38C2 has been conjugated to tumor-targeting carriers to hydrolyze prodrugs like derivatives, selectively killing human tumor cell lines such as colonic LoVo and reducing tumor burden in animal models of . Additionally, abzymes capable of cleaving tumor-associated peptides enhance immune recognition of cancer cells. These applications are predominantly preclinical, emphasizing abzymes' high specificity to reduce off-target effects relative to small-molecule chemotherapeutics.

Challenges and Prospects

Current Limitations

One major limitation of abzymes is their low catalytic , characterized by turnover numbers (k_cat) that are frequently below 1 s⁻¹, such as 0.031 s⁻¹ observed for certain ester-hydrolyzing abzymes. This represents a reduction of up to 10⁶-fold compared to natural enzymes, which typically achieve k_cat values in the range of 10 to 10⁴ s⁻¹ for similar reactions. The inefficiency stems primarily from the antibodies' evolutionary optimization for high-affinity substrate binding rather than rapid , resulting in slow product dissociation and limited rate enhancements of only 10² to 10⁵ relative to the uncatalyzed reaction—far short of the 10⁸ to 10¹² enhancements provided by enzymes. In therapeutic contexts, this necessitates high dosing or extended exposure times to process sufficient substrate, constraining practical applications. Another significant hurdle is , particularly for abzymes generated from non-human sources like hybridomas, which provoke () responses in patients. These immune reactions neutralize the abzyme's activity and can induce or anaphylactic effects, limiting repeated administrations. Even humanized variants, while reducing immunogenicity by incorporating frameworks, retain residual risks due to novel idiotypic determinants in the catalytic . This challenge underscores the need for fully human abzyme platforms, though current approaches have not fully resolved the issue for clinical . Production of abzymes presents substantial challenges, primarily due to the reliance on for monoclonal antibody generation, which is both expensive and inefficient. The process involves animal immunization with transition-state analogs, splenic B-cell fusion with myeloma cells, and laborious screening of thousands of clones to identify rare catalytic variants, often costing tens of thousands of dollars per successful abzyme. Low yields and the hit-or-miss nature of eliciting catalytic activity compound these difficulties, making scalable a persistent barrier despite advances in recombinant expression systems.

Future Directions

Recent advancements in computational design have leveraged (AI) and simulations to optimize the active sites of abzymes, addressing limitations in catalytic efficiency. Post-2020 efforts have integrated / () approaches with funnel to refine catalytic cores, such as the L-S35R mutant of A17, which achieved a 170-fold increase in efficiency for organophosphorus . algorithms, including deep neural networks, enable maturation by predicting turnover rates from data, facilitating de novo biocatalyst design. These tools, combined with of immunoglobulin repertoires, promise to accelerate the development of high-affinity abzymes for targeted reactions. Hybrid abzymes, formed through fusion with stabilizing moieties, represent a promising strategy to enhance thermal and operational stability while preserving catalytic function. Researchers have engineered fusions of catalytic antibodies with tags bearing high negative charge and low isoelectric points, resulting in hyper-stable variants suitable for therapeutic production. Chimeric constructs, such as single-chain variable fragments (scFvs) linked to fusion proteins, maintain antigen-binding and hydrolytic activity, as demonstrated in models where linker optimization preserved chorismate mutase-like . Although direct integrations with remain exploratory, these hybrid designs draw parallels to nanozyme systems, potentially extending abzyme durability in harsh environments. Gene therapy approaches offer a pathway for expression of abzymes, particularly for chronic neurodegenerative conditions like . Delivery of catalytic immunoglobulin genes via recombinant serotype 9 (rAAV9) into mouse models of amyloid-beta accumulation has shown prophylactic and therapeutic efficacy, reducing plaque load by 20-40% in the hippocampus without inducing or vascular issues. The expressed abzyme IgV L5D3 hydrolyzed amyloid-beta peptides into non-aggregative fragments, with widespread neuronal secretion confirmed in . This strategy circumvents immune responses associated with exogenous administration, positioning abzymes as long-term catalysts for clearance. As of 2025, ongoing research has focused on improving abzyme , with studies demonstrating enhanced stability and in single-domain catalytic antibodies through targeted , potentially addressing production and durability challenges. Additionally, catalytic antibodies have been implicated in conditions like and (ME/CFS), where they may contribute to tissue damage via myelin , opening prospects for diagnostic and therapeutic interventions. In broader , abzymes are gaining traction in for custom catalysts in synthesis, enabling selective activation and complex molecule assembly. Antibody-directed abzyme has been applied to convert inert precursors into cytotoxic agents at tumor sites, enhancing precision. These catalytic platforms support multi-step aldol reactions and nucleophilic displacements, mimicking natural cascades for scalable pharmaceutical production. By integrating with libraries, abzymes facilitate programmable biocatalysis, potentially revolutionizing the synthesis of high-value therapeutics.

References

  1. https://pmc.ncbi.nlm.nih.gov/articles/PMC9554387/
  2. https://doi.org/10.1126/science.3787262
  3. https://doi.org/10.1126/science.2727702
  4. https://doi.org/10.1074/jbc.M300870200
  5. https://journals.asm.org/doi/10.1128/mbio.00541-24
  6. https://www.tandfonline.com/doi/abs/10.1080/10426509608545133
  7. https://shokatlab.ucsf.edu/pdfs/2188666.pdf
  8. https://doi.org/10.1007/s12010-022-04183-1
  9. https://www.science.org/doi/10.1126/science.234.4783.1566
  10. https://www.science.org/doi/10.1126/science.8211138
  11. https://pubs.acs.org/doi/10.1021/ja973676b
  12. https://pubmed.ncbi.nlm.nih.gov/11385462/
  13. https://pubmed.ncbi.nlm.nih.gov/33918914/
  14. https://www.jstage.jst.go.jp/article/biochemistry1922/115/4/115_4_623/_pdf
  15. https://www.pnas.org/doi/10.1073/pnas.200360497
  16. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/catalytic-antibody
  17. https://pubs.acs.org/doi/10.1021/acs.biochem.3c00433
  18. https://biosci.mcdb.ucsb.edu/immunology/Antibody-Antigen/catab.htm
  19. https://www.nature.com/articles/nbt0391-258
  20. https://doi.org/10.1126/science.2672338
  21. https://pubmed.ncbi.nlm.nih.gov/11112840/
  22. https://pubmed.ncbi.nlm.nih.gov/9369225/
  23. https://pubmed.ncbi.nlm.nih.gov/34802738/
  24. https://www.mdpi.com/1422-0067/23/7/3898
  25. https://pmc.ncbi.nlm.nih.gov/articles/PMC2527403/
  26. https://pmc.ncbi.nlm.nih.gov/articles/PMC21481/
  27. https://www.sciencedirect.com/science/article/abs/pii/S1567576901000546
  28. https://www.pnas.org/doi/10.1073/pnas.93.2.799
  29. https://doi.org/10.1351/pac199668112009
  30. https://link.springer.com/content/pdf/10.1007/BF02821512.pdf
  31. https://pubmed.ncbi.nlm.nih.gov/12972259/
  32. https://doi.org/10.1007/BF02821512
  33. https://pmc.ncbi.nlm.nih.gov/articles/PMC8521504/
  34. https://onlinelibrary.wiley.com/doi/full/10.1002/ijch.202300078
  35. https://www.jbc.org/article/S0021-9258%2818%2936112-X/fulltext
  36. https://pmc.ncbi.nlm.nih.gov/articles/PMC4198531/
  37. https://pubmed.ncbi.nlm.nih.gov/39961023/
  38. https://pubmed.ncbi.nlm.nih.gov/38011893/
  39. https://link.springer.com/article/10.1007/s12010-022-04183-1
Add your contribution
Related Hubs
User Avatar
No comments yet.