SEMISYNTHETIC ENZYMES FROM ANTI HAPTEN ANTIBODIES

  • Tramontano, Alfonso, (PI)

Project: Research project

Description

A chemically modified antibody in which a reactive group is juxtaposed to
the binding site for a hapten may assume enzyme-like properties. The
binding to antibody may accelerate the reaction of a homologous or hapten
analog with the covalently linked species. We propose to use a chelated
zinc species or a flavin derivative, as examples of enzymic cofactors, for
the expression of hydrolysis or redox behavior respectively, in anti hapten
antibodies. A haloacetyl derivative of the cofactor may be
regioselectively incorporated into an antibody which is chemically
thiolated near the combining region. The required thiol group is
introduced in the correct position by an affinity labeling scheme using the
hapten to deliver a photoreactive, disulfide linked appendage. Photolysis
and disulfide reduction exposes the covalently linked thiol appendage. The
non-covalently bound hapten may be removed and the chemically modified
antibody that remains should serve for the production of enzyme-like
substances. Such modified antibodies might also be useful for the ligation
of probes for the investigation of antigen structure. The production of
artificial enzymes is a widespread effort which is being approached from
many directions. Advances in this area have great theoretical significance
as well as practical implications. Synthetic or semisynthetic enzymes may
eventually be useful for the treatment of disease, as diagnostic reagents,
or as industrial catalysts. The use of immunoglobulins as starting
materials for semisynthetic enzymes is a new approach, advanced here for
the first time.
StatusFinished
Effective start/end date9/24/852/28/94

Funding

  • National Institutes of Health: $190,852.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Catalytic Antibodies
Antibodies
Haptens
Hydrolysis
Catalysis
Amides
Enzymes
Labeling
Sulfhydryl Compounds
Ligands
Disulfides
Binding Sites
Organophosphonates
Catalysts
Derivatives
Amines
Esters
Complementary DNA
Amino Acids
Oxidation

Keywords

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)