Site-Specific Chemical Conjugation of Antibodies by Using Affinity Peptide for the Development of Therapeutic Antibody Format
Artificially modified IgG molecules are increasingly utilized in industrial and clinical applications. In the present study, the method of chemical conjugation by affinity peptide (CCAP) for site-specific chemical modification has been developed by using a peptide that bound with high affinity to hu...
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| Veröffentlicht in: | Bioconjugate chemistry 2019-03, Vol.30 (3), p.698-702 |
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| container_title | Bioconjugate chemistry |
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| creator | Kishimoto, Satoshi Nakashimada, Yuichi Yokota, Riri Hatanaka, Takaaki Adachi, Motoyasu Ito, Yuji |
| description | Artificially modified IgG molecules are increasingly utilized in industrial and clinical applications. In the present study, the method of chemical conjugation by affinity peptide (CCAP) for site-specific chemical modification has been developed by using a peptide that bound with high affinity to human IgG-Fc. This method enabled a rapid modification of a specific residue (Lys248 on Fc) in a one-step reaction under mild condition to form a stable amide bond between the peptide and Fc. The monovalent peptide-IgG conjugate not only maintained complete antigen binding but also bound to Fc receptors (FcRn, FcγRI, and FcγRIIIa), indicating that it is a suitable conjugate form that can be further developed into highly functional antibody therapeutics. CCAP was applied for the preparation of an antibody-drug conjugate and a bispecific antibody to demonstrate the usefulness of this method. |
| doi_str_mv | 10.1021/acs.bioconjchem.8b00865 |
| format | Article |
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In the present study, the method of chemical conjugation by affinity peptide (CCAP) for site-specific chemical modification has been developed by using a peptide that bound with high affinity to human IgG-Fc. This method enabled a rapid modification of a specific residue (Lys248 on Fc) in a one-step reaction under mild condition to form a stable amide bond between the peptide and Fc. The monovalent peptide-IgG conjugate not only maintained complete antigen binding but also bound to Fc receptors (FcRn, FcγRI, and FcγRIIIa), indicating that it is a suitable conjugate form that can be further developed into highly functional antibody therapeutics. 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In the present study, the method of chemical conjugation by affinity peptide (CCAP) for site-specific chemical modification has been developed by using a peptide that bound with high affinity to human IgG-Fc. This method enabled a rapid modification of a specific residue (Lys248 on Fc) in a one-step reaction under mild condition to form a stable amide bond between the peptide and Fc. The monovalent peptide-IgG conjugate not only maintained complete antigen binding but also bound to Fc receptors (FcRn, FcγRI, and FcγRIIIa), indicating that it is a suitable conjugate form that can be further developed into highly functional antibody therapeutics. CCAP was applied for the preparation of an antibody-drug conjugate and a bispecific antibody to demonstrate the usefulness of this method.</description><subject>Affinity</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies - chemistry</subject><subject>Antibodies - therapeutic use</subject><subject>Antigens</subject><subject>Bispecific antibodies</subject><subject>Chemical modification</subject><subject>Conjugates</subject><subject>Conjugation</subject><subject>Fc receptors</subject><subject>Humans</subject><subject>Immunoconjugates - chemistry</subject><subject>Immunoglobulin A - chemistry</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - chemistry</subject><subject>Organic chemistry</subject><subject>Peptides</subject><subject>Peptides - chemistry</subject><subject>Receptors</subject><subject>Rodentia</subject><subject>Therapeutic applications</subject><subject>Trastuzumab - chemistry</subject><subject>Trastuzumab - therapeutic use</subject><issn>1043-1802</issn><issn>1520-4812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9rFDEYh4NYbG39Chrw4mW2-TuTOS6rVaFgoe05ZDJvullmJmOSKezB726WXYt4kRze8PL8ngR-CH2gZEUJo9fGplXngw3Tzm5hXKmOEFXLV-iCSkYqoSh7Xe5E8Ioqws7R25R2hJCWKvYGnXNSl0P5Bfp17zNU9zNY77zFmyLz1gx4U8zLk8k-TDg4vJ6y70LvIeFujx-Tn57w2jk_-bzHdzBn3wN2IeK8BfwZnmEI8whTPmQfthDNDEsu_pNnj29CHE2-QmfODAneneYlerz58rD5Vt3--Pp9s76tjGhlrmoGdV0r2jhlVaN60vauZ1IJBlJS0YCV1AnRtr2UtRCWGl6XrTJdQ1zDCb9En47eOYafC6SsR58sDIOZICxJM1oL0rZctAX9-A-6C0ucyu80Y4JyJjlvCtUcKRtDShGcnqMfTdxrSvShIV0a0n81pE8NleT7k3_pRuhfcn8qKQA_AgfDy9v_0_4GjJ-ibg</recordid><startdate>20190320</startdate><enddate>20190320</enddate><creator>Kishimoto, Satoshi</creator><creator>Nakashimada, Yuichi</creator><creator>Yokota, Riri</creator><creator>Hatanaka, Takaaki</creator><creator>Adachi, Motoyasu</creator><creator>Ito, Yuji</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5239-5070</orcidid></search><sort><creationdate>20190320</creationdate><title>Site-Specific Chemical Conjugation of Antibodies by Using Affinity Peptide for the Development of Therapeutic Antibody Format</title><author>Kishimoto, Satoshi ; Nakashimada, Yuichi ; Yokota, Riri ; Hatanaka, Takaaki ; Adachi, Motoyasu ; Ito, Yuji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a495t-62e666817f8c878d09dfd25842e55147ec51f4499d55644c1a3647e8ab70f7303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Affinity</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies - chemistry</topic><topic>Antibodies - therapeutic use</topic><topic>Antigens</topic><topic>Bispecific antibodies</topic><topic>Chemical modification</topic><topic>Conjugates</topic><topic>Conjugation</topic><topic>Fc receptors</topic><topic>Humans</topic><topic>Immunoconjugates - chemistry</topic><topic>Immunoglobulin A - chemistry</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin G - chemistry</topic><topic>Organic chemistry</topic><topic>Peptides</topic><topic>Peptides - chemistry</topic><topic>Receptors</topic><topic>Rodentia</topic><topic>Therapeutic applications</topic><topic>Trastuzumab - chemistry</topic><topic>Trastuzumab - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kishimoto, Satoshi</creatorcontrib><creatorcontrib>Nakashimada, Yuichi</creatorcontrib><creatorcontrib>Yokota, Riri</creatorcontrib><creatorcontrib>Hatanaka, Takaaki</creatorcontrib><creatorcontrib>Adachi, Motoyasu</creatorcontrib><creatorcontrib>Ito, Yuji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Bioconjugate chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kishimoto, Satoshi</au><au>Nakashimada, Yuichi</au><au>Yokota, Riri</au><au>Hatanaka, Takaaki</au><au>Adachi, Motoyasu</au><au>Ito, Yuji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Site-Specific Chemical Conjugation of Antibodies by Using Affinity Peptide for the Development of Therapeutic Antibody Format</atitle><jtitle>Bioconjugate chemistry</jtitle><addtitle>Bioconjugate Chem</addtitle><date>2019-03-20</date><risdate>2019</risdate><volume>30</volume><issue>3</issue><spage>698</spage><epage>702</epage><pages>698-702</pages><issn>1043-1802</issn><eissn>1520-4812</eissn><abstract>Artificially modified IgG molecules are increasingly utilized in industrial and clinical applications. In the present study, the method of chemical conjugation by affinity peptide (CCAP) for site-specific chemical modification has been developed by using a peptide that bound with high affinity to human IgG-Fc. This method enabled a rapid modification of a specific residue (Lys248 on Fc) in a one-step reaction under mild condition to form a stable amide bond between the peptide and Fc. The monovalent peptide-IgG conjugate not only maintained complete antigen binding but also bound to Fc receptors (FcRn, FcγRI, and FcγRIIIa), indicating that it is a suitable conjugate form that can be further developed into highly functional antibody therapeutics. 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| ispartof | Bioconjugate chemistry, 2019-03, Vol.30 (3), p.698-702 |
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| source | ACS Publications; MEDLINE |
| subjects | Affinity Animals Antibodies Antibodies - chemistry Antibodies - therapeutic use Antigens Bispecific antibodies Chemical modification Conjugates Conjugation Fc receptors Humans Immunoconjugates - chemistry Immunoglobulin A - chemistry Immunoglobulin G Immunoglobulin G - chemistry Organic chemistry Peptides Peptides - chemistry Receptors Rodentia Therapeutic applications Trastuzumab - chemistry Trastuzumab - therapeutic use |
| title | Site-Specific Chemical Conjugation of Antibodies by Using Affinity Peptide for the Development of Therapeutic Antibody Format |
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