Abstract
Inhibiting individual MMPs of biomedical importance with high selectivity is critical for both fundamental research and therapy development. Here we describe the methods for discovery of inhibitory monoclonal antibodies from synthetic human antibody phage display libraries carrying convex paratopes encoded by long complementarity-determining region (CDR)-H3 segments. We demonstrate the application of this technique for isolation of highly specific and potent antibody inhibitors of human MMP-14.
Keywords:
Convex paratope; Inhibitory antibody; Long CDR; Synthetic library.
MeSH terms
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Antibodies, Monoclonal / genetics
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Antibodies, Monoclonal / immunology*
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Antibodies, Monoclonal / pharmacology
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Binding Sites, Antibody / immunology
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Complementarity Determining Regions / immunology
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Drug Discovery / methods*
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Immunoglobulin Fab Fragments / genetics
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Immunoglobulin Fab Fragments / immunology
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Immunoglobulin Fab Fragments / pharmacology
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Matrix Metalloproteinase 14 / immunology*
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Matrix Metalloproteinase Inhibitors / immunology*
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Matrix Metalloproteinase Inhibitors / pharmacology
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Peptide Library*
Substances
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Antibodies, Monoclonal
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Complementarity Determining Regions
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Immunoglobulin Fab Fragments
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Matrix Metalloproteinase Inhibitors
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Peptide Library
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MMP14 protein, human
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Matrix Metalloproteinase 14