A new algorithm to convert a normal antibody into the corresponding catalytic antibody

Over thousands of monoclonal antibodies (mAbs) have been produced so far, and it would be valuable if these mAbs could be directly converted into catalytic antibodies. We have designed a system to realize the above concept by deleting Pro95, a highly conserved residue in CDR-3 of the antibody light chain. The deletion of Pro95 is a key contributor to catalytic function of the light chain. The S35 and S38 light chains have identical amino acid sequences except for Pro95. The former, with Pro95 did not show any catalytic activity, whereas the latter, without Pro95, exhibited peptidase activity. To verify the generality of this finding, we tested another light chain, T99wt, which had Pro95 and showed little catalytic activity. In contrast, a Pro95-deleted mutant enzymatically degraded the peptide substrate and amyloid-beta molecule. These two cases demonstrate the potential for a new method of creating catalytic antibodies from the corresponding mAbs.

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New technologies to introduce a catalytic function into antibodies: A unique human catalytic antibody light chain showing degradation of β-amyloid molecule along with the peptidase activity

FASEB BioAdvances ◽

10.1096/fba.1025 ◽

2019 ◽

Vol 1 (2) ◽

pp. 93-104

Author(s):

Emi Hifumi ◽

Hiroaki Taguchi ◽

Eiichi Toorisaka ◽

Taizo Uda

Keyword(s):

Light Chain ◽

New Technologies ◽

Catalytic Antibody ◽

Peptidase Activity ◽

Catalytic Function ◽

Β Amyloid

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Presence of Catalytic Activity of the Antibody Light Chain Raised against Complementarity Determining Region Peptide of Super Catalytic Antibody

ACS Symposium Series - Biological Systems Engineering ◽

10.1021/bk-2002-0830.ch016 ◽

2002 ◽

pp. 200-208 ◽

Cited By ~ 2

Author(s):

Y. Zhou ◽

E. Hifumi ◽

H. Kondo ◽

T. Uda

Keyword(s):

Catalytic Activity ◽

Light Chain ◽

Catalytic Antibody ◽

Complementarity Determining Region

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Comparison of the amino acid sequences of the variable regions of light chains derived from two homogeneous rabbit anti-pneumococcal antibodies

Biochemical Journal ◽

10.1042/bj1410015 ◽

1974 ◽

Vol 141 (1) ◽

pp. 15-25 ◽

Cited By ~ 18

Author(s):

Jean-Claude Jaton

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Light Chain ◽

Amino Acid Sequences ◽

Basic Sequence ◽

Light Chains ◽

Amino Acid Residues ◽

Rabbit Antibody ◽

Variable Regions ◽

Type Iii

The amino acid sequence of the N-terminal 139 residues of the L (light) chain derived from a homogeneous rabbit antibody to type III pneumococci was determined. This L chain, designated BS-5, exhibits a greater degree of homology with the basic sequence of human κ chains of subgroup I (72%) than with subgroups II and III. L-chain BS-5 differs from another L chain (BS-1), also derived from an antibody to type III pneumococci (Jaton, 1974), by eight amino acid residues, even though the chains are identical within the N-terminal 30 residues. Six of these eight substitutions are located within the three hypervariable sections of the variable half: Asn/Ser in position 31, Glu/Ala in position 55, Asx/Thr, Thr/Gly, Thr/Gly and Val/Tyr in positions 92, 94, 96 and 97 respectively. The two anti-pneumococcal L chains BS-1 and BS-5 are much more similar to each other than to an anti-azobenzoate L chain (Appella et al., 1973), from which they differ by 30 and 29 residues respectively. Of these interchanges 13–15 are confined to the three hypervariable sections, and 11 occur within the N-terminal 27 positions. The three chains have an identical sequence from residue 98 to residue 139, except for a possible inversion of two residues in positions 130–131 of the anti-azobenzoate chain.

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Monoclonal anti-light chain idiotype as a tumor-specific probe for human neoplastic B lymphocytes

Blood ◽

10.1182/blood.v69.3.919.919 ◽

1987 ◽

Vol 69 (3) ◽

pp. 919-923 ◽

Cited By ~ 4

Author(s):

M Wrightham ◽

AL Tutt ◽

MJ Glennie ◽

TJ Hamblin ◽

GT Stevenson ◽

...

Keyword(s):

B Cell ◽

Tumor Cells ◽

B Lymphocytes ◽

Light Chain ◽

Normal Serum ◽

Lymphocytic Leukemia ◽

Light Chains ◽

Specific Probe ◽

Tonsillar Cells ◽

Binding Curves

Abstract Tumor cells from patients with B cell neoplasms often secrete small amounts of free monoclonal light chains that can be found in the urine. Such tumor-derived light chains of the lambda type from a patient with typical chronic lymphocytic leukemia have been used to raise mouse monoclonal antibodies (MoAbs). A hybridoma-secreting antibody that recognized the idiotypic lambda chain but not normal lambda chains by a preliminary screen but which also reacted with idiotypic IgM from the patient's tumor cells was selected. This MoAb in fact recognized 1 in 20 X 10(3) molecules of pooled normal lambda chains, thus establishing its specificity for a private idiotypic determinant. It failed to give a detectable reaction with normal IgM, normal serum, or a panel of IgM paraproteins. The antibody bound to the patient's neoplastic B cells but not to normal tonsillar cells. The site of binding of the antibody to idiotypic IgM is clearly separate from that of another MoAb specific for idiotypic determinants on heavy plus light chains, since the two showed additive binding curves. The determinant also appeared to be less available in dimeric lambda chains than in monomeric lambda chains or in idiotypic IgM. Antibodies to idiotypic determinants on light chains show some technical advantages and should be useful for monitoring and possibly treating B cell tumors, either alone or together with the more conventional anti-idiotypic antibodies that usually recognize the heavy and light chain combination.

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