Autoantibodies which enhance the rate of a chemical reaction

Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,...

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4241431, 4241751, 424 941, 4351885, A61K 39395, C12N 900

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active

055995381

ABSTRACT:
Autoantibodies which enhance the rate of a chemical reaction of a substrate, processes for their preparation, their use and compositions thereof are disclosed. In particular, an autoantibody capable of catalyzing the hydrolysis of the peptide bond between amino acid residues 16 and 17 in the neurotransmitter vasoactive intestinal peptide (VIP) is disclosed. Human anti-thyroglobulin antibodies isolated by chromatography on protein-A and immobilized Tg hydrolyzed radiolabeled Tg, as shown by generation of several lower-sized products on SDS-electrophoresis gels. The activity displayed a K.sub.m value of a 39 nM property typical of an antibody-combining site. Tg-antibodies also hydrolyzed commercially available peptidyl-methylcoumarinamide (MCA) substrates, displaying a preference for arg-MCA and lys-MCA containing conjugates. The hydrolysis of pro-phe-arg-MCA was characterized by K.sub.m (17 .mu.M) and k.sub.cat 0.06 min.sup.-1. Peptidyl-MCA hydrolysis was inhibited potently by thyroglobulin (K.sub.i 24 nM), suggesting a catalytic site/located in the antibody combining site. In control experiments, the hydrolytic activities were removed by immunoadsorption with immobilized anti-human IgG, and IgG depleted of the Tg-specific antibodies by affinity chromatography did not display Tg and pro-phe-arg-MCA hydrolyzing activities.

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