ArticleThe Journal of biological chemistry2008
Exceptional amyloid beta peptide hydrolyzing activity of nonphysiological immunoglobulin variable domain scaffolds.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States.International journal of molecular sciences · 2020Pooled it
- Physiological IgM class catalytic antibodies selective for transthyretin amyloid.The Journal of biological chemistry · 2014Trial
- Constitutive production of catalytic antibodies to a Staphylococcus aureus virulence factor and effect of infection.The Journal of biological chemistry · 2012Trial
- Role of Copper and Zinc Ions in the Hydrolytic Degradation of Neurodegeneration-Related Peptides.Molecules (Basel, Switzerland) · 2025Article
- Obtaining Highly Active Catalytic Antibodies Capable of Enzymatically Cleaving Antigens.International journal of molecular sciences · 2022Article
- Evaluating Combined Precursor Isotopic Labeling and Isobaric Tagging Performance on Orbitraps To Study the Peripheral Proteome of Alzheimer's Disease.Analytical chemistry · 2020Article
- Catalytic antibody (catabody) platform for age-associated amyloid disease: From Heisenberg's uncertainty principle to the verge of medical interventions.Mechanisms of ageing and development · 2020Review
- New technologies to introduce a catalytic function into antibodies: A unique human catalytic antibody light chain showing degradation of β-amyloid molecule along with the peptidase activity.FASEB bioAdvances · 2019Article
- Amyloid beta: structure, biology and structure-based therapeutic development.Acta pharmacologica Sinica · 2017Review
- Specific amyloid β clearance by a catalytic antibody construct.The Journal of biological chemistry · 2015Article
- Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer's disease: prophylactic and therapeutic applications.Molecular neurobiology · 2015Article
- Metal-dependent amyloid β-degrading catalytic antibody construct.Journal of biotechnology · 2014Article
- Antibodies to a superantigenic glycoprotein 120 epitope as the basis for developing an HIV vaccine.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Constant domain-regulated antibody catalysis.The Journal of biological chemistry · 2012Article
- Proteolytic degradation of amyloid β-protein.Cold Spring Harbor perspectives in medicine · 2012Review
- Alzheimer's disease: a pathogenetic autoimmune disorder caused by herpes simplex in a gene-dependent manner.International journal of Alzheimer's disease · 2010Article
- Soluble artificial metalloproteases with broad substrate selectivity, high reactivity, and high thermal and chemical stabilities.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2010Article
- Immunological origin and functional properties of catalytic autoantibodies to amyloid beta peptide.Journal of clinical immunology · 2010Review
- Antigen-specific proteolysis by hybrid antibodies containing promiscuous proteolytic light chains paired with an antigen-binding heavy chain.The Journal of biological chemistry · 2009Article
- Article
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Authors and funding
7 authors.
Funding
Abstract
Nucleophilic sites in the paired variable domains of the light and heavy chains (VL and VH domains) of Ig can catalyze peptide bond hydrolysis. Amyloid beta (Abeta)-binding Igs are under consideration for immunotherapy of Alzheimer disease. We searched for Abeta-hydrolyzing human IgV domains (IgVs) in a library containing a majority of single chain Fv clones mimicking physiological VL-VH-combining sites and minority IgV populations with nonphysiological structures generated by cloning errors. Random screening and covalent selection of phage-displayed IgVs with an electrophilic Abeta analog identified rare IgVs that hydrolyzed Abeta mainly at His14-Gln15. Inhibition of IgV catalysis and irreversible binding by an electrophilic hapten suggested a nucleophilic catalytic mechanism. Structural analysis indicated that the catalytic IgVs are nonphysiological structures, a two domain heterodimeric VL (IgVL2-t) and single domain VL clones with aberrant polypeptide tags (IgVL-t'). The IgVs hydrolyzed Abeta at rates superior to naturally occurring Igs by 3-4 orders of magnitude. Forced pairing of the single domain VL with VH or VL domains resulted in reduced Abeta hydrolysis, suggesting catalysis by the unpaired VL domain.Angstrom level amino acid displacements evident in molecular models of the two domain and unpaired VL domain clones explain alterations of catalytic activity. In view of their superior catalytic activity, the VL domain IgVs may help attain clearance of medically important antigens more efficiently than natural Igs.
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