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#catalytic antibodies

3 public questions tagged with this topic.

Immunological Applications

The prodrug in abzyme therapy is:

Abzyme-directed prodrug therapy also known as ADAPT aims to combine tumor-targeting specificity of antibodies with catalytic turnover allowing one antibody molecule to activate many prodrug molecules amplifying effect. Conventional systemic chemotherapy distributes throughout body causing dose limiting myelosuppression, alopecia, mucositis due to toxicity to rapidly dividing normal tissues such as bone marrow and gastrointestinal epithelium. Prodrug strategy masks cytotoxic warhead with cleavable moiety ester, carbamate, glucuronide, or phosphate rendering molecule 100 to 1000 fold less toxic,

Ref: Shabat et al PNAS 1995 ADAPT abzyme prodrug site activation; US Patent 5948647 antibody directed prodrug therapy.

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Immunological Applications

Abzymes are antibodies that:

Catalytic antibodies termed abzymes represent attempt to harness immune binding energy for chemical transformation similar to enzymes that accelerate reactions 10^10 fold by stabilizing transition state through complementarity. Natural enzymes use preorganized active site residues histidine, aspartate, serine triad precisely positioned via folding to provide general acid-base, nucleophile, oxyanion hole stabilization. Abzymes generated by immunization with stable transition-state analogue designed to mimic high energy tetrahedral intermediate of ester hydrolysis such as phosphonate monoester w

Ref: Lerner et al Science 1991 252:659 catalytic antibodies abzyme; Shabat et al Transition state analog phosphonate ester.

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Immunological Applications

Abzymes are antibodies that:

Abzymes catalytic antibodies merge Ig antigen-binding specificity enzyme-like rate acceleration accelerating chemical transformations difficult natural enzymes. Generation exploits transition state analog theory Pauling: enzyme binds transition state tighter substrate lowering activation energy. Immunization stable mimic tetrahedral high-energy intermediate ester hydrolysis phosphonate ester phosphorus replacing carbon maintaining tetrahedral but stable replaces labile carbonyl elicits immune response producing antibodies binding pocket complementary transition state geometry providing binding

Ref: Tramontano Science 1986 Abzyme Catalytic Antibody First Demonstration; Lerner Chem Review Abzymes Concept 1992; Janeway Abzyme Catalytic Activity Binding Energy Chapter 5.

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