Inhibition of hepatitis C virus NS3 protease by peptides derived from complementarity‐determining regions (CDRs) of the monoclonal antibody 8D4: tolerance of a CDR peptide to conformational changes of a target
Copyright policy )Inhibition of hepatitis C virus NS3 protease by peptides derived from complementarity‐determining regions (CDRs) of the monoclonal antibody 8D4: tolerance of a CDR peptide to conformational changes of a target
We have synthesized and characterized peptides derived from complementarity‐determining regions (CDRs) of 8D4, a mouse monoclonal antibody against NS3 protease domain of hepatitis C virus. 8D4 inhibits enzymatic activity without its cofactor, NS4A peptide. One of the synthetic peptides derived from CDRs, CDR1 of the heavy‐chain (CDR‐H1) peptide strongly inhibited NS3 protease activity competitively in the absence of NS4A and non‐competitively in the presence of NS4A. Moreover, cyclic CDR‐H1 peptides bridged by disulfide inhibited NS3 protease more potently. The chain length of the CDR‐H1 peptide is critical for strong inhibition, even when the peptide is circularized. This finding suggests the importance of peptide conformation. In contrast to a cognate antibody molecule, CDR‐derived peptides may provide good ligands for target molecules by having a tolerance to conformational changes of the targets caused by cofactor binding or mutation.
- Tohoku University Japan
CDR peptide, Protein Conformation, Molecular Sequence Data, Antibodies, Monoclonal, Viral Nonstructural Proteins, Conformational change, Ligands, Binding, Competitive, Complementarity Determining Regions, Peptides, Cyclic, Peptide Fragments, Enzyme Activation, Kinetics, Structure-Activity Relationship, Amino Acid Sequence, Circularization, Antibody, NS3 protease, Protein Binding
CDR peptide, Protein Conformation, Molecular Sequence Data, Antibodies, Monoclonal, Viral Nonstructural Proteins, Conformational change, Ligands, Binding, Competitive, Complementarity Determining Regions, Peptides, Cyclic, Peptide Fragments, Enzyme Activation, Kinetics, Structure-Activity Relationship, Amino Acid Sequence, Circularization, Antibody, NS3 protease, Protein Binding
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