Post-translational structural modifications of immunoglobulin G and their effect on biological activity
The size, heterogeneity, and biological production process of protein therapeutics like monoclonal antibodies create unique challenges for their analysis and regulation compared with small molecules. Complete structural characterization of a molecule 1000-fold heavier than aspirin is no small feat....
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| Veröffentlicht in: | Analytical and bioanalytical chemistry 2015, Vol.407 (1), p.79-94 |
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| creator | Hmiel, Laura K. Brorson, Kurt A. Boyne, Michael T. |
| description | The size, heterogeneity, and biological production process of protein therapeutics like monoclonal antibodies create unique challenges for their analysis and regulation compared with small molecules. Complete structural characterization of a molecule 1000-fold heavier than aspirin is no small feat. Biological post-translational modifications such as glycosylation further complicate their characterization and regulation. Even approved protein therapeutics are known to contain multiple structural variants in differing amounts. Structural modification occurs during production and storage as well as within patients after administration. Thus, the goals of manufacturers and regulators are to control and characterize this heterogeneity, not take on the impossible task of eliminating it. The aim of this review is to describe the structural heterogeneities known to occur with immunoglobulin G (IgG), note current detection and analytical strategies, establish their causes, and define their potential effects on the ultimate safety, purity, and potency of antibody therapeutics when known. |
| doi_str_mv | 10.1007/s00216-014-8108-x |
| format | Article |
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Complete structural characterization of a molecule 1000-fold heavier than aspirin is no small feat. Biological post-translational modifications such as glycosylation further complicate their characterization and regulation. Even approved protein therapeutics are known to contain multiple structural variants in differing amounts. Structural modification occurs during production and storage as well as within patients after administration. Thus, the goals of manufacturers and regulators are to control and characterize this heterogeneity, not take on the impossible task of eliminating it. 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Complete structural characterization of a molecule 1000-fold heavier than aspirin is no small feat. Biological post-translational modifications such as glycosylation further complicate their characterization and regulation. Even approved protein therapeutics are known to contain multiple structural variants in differing amounts. Structural modification occurs during production and storage as well as within patients after administration. Thus, the goals of manufacturers and regulators are to control and characterize this heterogeneity, not take on the impossible task of eliminating it. The aim of this review is to describe the structural heterogeneities known to occur with immunoglobulin G (IgG), note current detection and analytical strategies, establish their causes, and define their potential effects on the ultimate safety, purity, and potency of antibody therapeutics when known.</description><subject>Analysis</subject><subject>Analytical Chemistry</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Biological</subject><subject>Characterization and Evaluation of Materials</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Control</subject><subject>Food Science</subject><subject>Glycosylation</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - chemistry</subject><subject>Immunoglobulin G - genetics</subject><subject>Immunoglobulin G - metabolism</subject><subject>Immunoglobulin G - therapeutic use</subject><subject>Immunoglobulins</subject><subject>Laboratory Medicine</subject><subject>Mathematical analysis</subject><subject>Monitoring/Environmental Analysis</subject><subject>Monoclonal antibodies</subject><subject>Protein Processing, Post-Translational</subject><subject>Proteins</subject><subject>Review</subject><subject>Strategy</subject><issn>1618-2642</issn><issn>1618-2650</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkk1vFiEQxzdGY1_0A3gxJF68bJ2BXZY9No3WJk30oGfCsrDSsFCBNe23l8en1pdo0nBgwvz-wwz8m-YFwgkCDG8yAEXeAnatQBDtzaPmEDmKlvIeHt_HHT1ojnK-AsBeIH_aHNCeQi0Ah83yMebSlqRC9qq4GJQnuaRNly3VcI2zs07_yGQSLXHruoW4-Dht3gVyTlSYSfliXCLGWqMLiYFMLvq4VJknShf3zZXbZ80Tq3w2z-_24-bzu7efzt63lx_OL85OL1vdd7S0kxgoAw1m6ufR1iEZ0BlFbVZrRoENoIyeRiZmtHRmk645Nhkq0ExCzYYdN6_3da9T_LqZXOTqsjbeq2DiliVyAV3XU4oPQIdh5AOM8AC0Q9HzceAVffUXehW3VJ-1UkPfcQbI6C9qUd5IF2ysX6B3ReVphzBwIfju2pN_UHXNZnU6BmNdPf9DgHuBTjHnZKy8Tm5V6VYiyJ1l5N4yslpG7iwjb6rm5V3D27Sa-V7x0yMVoHsg11RYTPptov9W_Q4kd8qD</recordid><startdate>2015</startdate><enddate>2015</enddate><creator>Hmiel, Laura K.</creator><creator>Brorson, Kurt A.</creator><creator>Boyne, Michael T.</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H8D</scope><scope>H8G</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>7QH</scope><scope>7T5</scope><scope>7UA</scope><scope>H94</scope></search><sort><creationdate>2015</creationdate><title>Post-translational structural modifications of immunoglobulin G and their effect on biological activity</title><author>Hmiel, Laura K. ; Brorson, Kurt A. ; Boyne, Michael T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c542t-b87230c0eb5d9f100302d18000cc320370aecb938d1f2d3bc1803be281eb8ade3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Analysis</topic><topic>Analytical Chemistry</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Biochemistry</topic><topic>Biological</topic><topic>Characterization and Evaluation of Materials</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Control</topic><topic>Food Science</topic><topic>Glycosylation</topic><topic>Heterogeneity</topic><topic>Humans</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin G - chemistry</topic><topic>Immunoglobulin G - genetics</topic><topic>Immunoglobulin G - metabolism</topic><topic>Immunoglobulin G - therapeutic use</topic><topic>Immunoglobulins</topic><topic>Laboratory Medicine</topic><topic>Mathematical analysis</topic><topic>Monitoring/Environmental Analysis</topic><topic>Monoclonal antibodies</topic><topic>Protein Processing, Post-Translational</topic><topic>Proteins</topic><topic>Review</topic><topic>Strategy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hmiel, Laura K.</creatorcontrib><creatorcontrib>Brorson, Kurt A.</creatorcontrib><creatorcontrib>Boyne, Michael T.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Materials science collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - 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Complete structural characterization of a molecule 1000-fold heavier than aspirin is no small feat. Biological post-translational modifications such as glycosylation further complicate their characterization and regulation. Even approved protein therapeutics are known to contain multiple structural variants in differing amounts. Structural modification occurs during production and storage as well as within patients after administration. Thus, the goals of manufacturers and regulators are to control and characterize this heterogeneity, not take on the impossible task of eliminating it. 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| subjects | Analysis Analytical Chemistry Animals Antibodies Biochemistry Biological Characterization and Evaluation of Materials Chemistry Chemistry and Materials Science Control Food Science Glycosylation Heterogeneity Humans Immunoglobulin G Immunoglobulin G - chemistry Immunoglobulin G - genetics Immunoglobulin G - metabolism Immunoglobulin G - therapeutic use Immunoglobulins Laboratory Medicine Mathematical analysis Monitoring/Environmental Analysis Monoclonal antibodies Protein Processing, Post-Translational Proteins Review Strategy |
| title | Post-translational structural modifications of immunoglobulin G and their effect on biological activity |
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