Nucleophilic proteolytic antibodies |
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Authors: | Gennady Gololobov Alfonso Tramontano Sudhir Paul |
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Institution: | (1) Department of Pathology and Laboratory Medicine, University of Texas Houston Medical School, 6431 Fannin, 77030 Houston, TX |
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Abstract: | Proteolytic antibodies appear to utilizecatalytic mechanisms akin to nonantibody serine proteases, assessed from mutagenesis
and protease-inhibitor studies. The catalytic efficiency derives substantially from the ability to recognize the ground state
with high affinity. Because the proteolytic activity is germline-encoded, catalysts with specificity for virtually any target
polypeptide could potentially be developed by applying appropriate immunogens and selection strategies. Analysis of transition-state
stabilizing interactions suggests that chemical reactivity ofactive-site serine residues is an important contributor to catalysis.
A prototype antigen analog capable of reacting covalently with nucleophilic serine residues permitted enrichment of the catalysts
from a phage-displayed lupus light-chain library. Further mechanistic developments in understanding proteolytic antibodies
may lead to the isolation of catalysts suitable for passive immunotherapy of major diseases, and elicitation of catalytic
immunity as a component of prophylactic vaccination. |
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Keywords: | Catalytic antibodies phage display serine proteases |
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