Conformational characterization of a novel anti-HER2 candidate antibody
Regulatory agencies establish that a broad physicochemical and biological characterization is necessary for the evaluation of comparability between a biosimilar candidate product and a reference commercial drug. Between them, conformational characterization of proteins is of vital importance to dete...
Gespeichert in:
| Veröffentlicht in: | PloS one 2019-05, Vol.14 (5), p.e0215442-e0215442 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0215442 |
|---|---|
| container_issue | 5 |
| container_start_page | e0215442 |
| container_title | PloS one |
| container_volume | 14 |
| creator | Moro Pérez, Leina Rodríguez Taño, Azalia de la Caridad Martín Márquez, Lázaro Roberto Gómez Pérez, Jose Alberto Valle Garay, Aisel Blanco Santana, Rancés |
| description | Regulatory agencies establish that a broad physicochemical and biological characterization is necessary for the evaluation of comparability between a biosimilar candidate product and a reference commercial drug. Between them, conformational characterization of proteins is of vital importance to determine its folding and biological functions. In this work, the conformational features of a novel monoclonal antibody (called 5G4) were evaluated by means of circular dichroism spectroscopy and fluorescence. Secondary structure and thermal stability of mAbs were determined by circular dichroism in the far ultraviolet, while three-dimensional folding of proteins was analyzed by both circular dichroism in the near ultraviolet and intrinsic tryptophan fluorescence. In all experiments, Herceptin (Roche) was used as control. Both antibodies showed a composition of secondary structure predominantly of β-sheets (55-56%) and thermal stability of ~ 75°C, suggesting structural similarity. The three-dimensional folding of proteins was also similar due to the absorption spectra of the aromatic residues and the emission wavelength maxima by fluorescence were comparable. The values of the fluorescence attenuation constant (Stern-Volmer constant) for increasing concentrations of acrylamide were also similar, suggesting a degree of exposure of tryptophan residues similar, although it was slightly decreased for Herceptin. Our data permit to consider that 5G4 monoclonal antibody showed similar conformational characteristics when compared with Herceptin. |
| doi_str_mv | 10.1371/journal.pone.0215442 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2222682685</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A584928774</galeid><doaj_id>oai_doaj_org_article_20412e33349040f6ad3b5e682c9adfaf</doaj_id><sourcerecordid>A584928774</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-65e698f519693608b491823ecc9c4716e38ab4a59e528a2322dc9197fe16d3b33</originalsourceid><addsrcrecordid>eNqNkl1r2zAUhs3YWLts_2BshsHYLpLpy7J0MyihawOFQvdxK05kOVFwrFSSy7pfPzlxSzx6Mctgc_Sc9-gcvVn2FqMZpiX-snGdb6GZ7VxrZojggjHyLDvFkpIpJ4g-P_o_yV6FsEGooILzl9kJxajEGOHT7GLu2tr5LUTrklqu1-BBR-Ptn30od3UOeevuTJNDG-308vyG5BraylYQzT62dNX96-xFDU0wb4bvJPv57fzH_HJ6dX2xmJ9dTTWXJE55YbgUdYEll5QjsWQSC0KN1lKzEnNDBSwZFNIURAChhFRaYlnWBvOKLimdZO8PurvGBTXMICiSHi7SWyRicSAqBxu183YL_l45sGofcH6lwEerG6MIYpgYSimTiKGaQyqRDiiIllDVUCetr0O1brk1lTZt9NCMRMc7rV2rlbtTvECiTIOfZJ8GAe9uOxOi2tqgTdNAa1zXn5tiybDAfWcf_kGf7m6gVpAasOnuUl3di6qzQjBJRFmyRM2eoNKqzNbqZJjapvgo4fMoITHR_I4r6EJQi-83_89e_xqzH4_YtYEmroNrut5aYQyyA6i9C8Gb-nHIGKne7w_TUL3f1eD3lPbu-IIekx4MTv8Cfkn4mg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2222682685</pqid></control><display><type>article</type><title>Conformational characterization of a novel anti-HER2 candidate antibody</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Moro Pérez, Leina ; Rodríguez Taño, Azalia de la Caridad ; Martín Márquez, Lázaro Roberto ; Gómez Pérez, Jose Alberto ; Valle Garay, Aisel ; Blanco Santana, Rancés</creator><creatorcontrib>Moro Pérez, Leina ; Rodríguez Taño, Azalia de la Caridad ; Martín Márquez, Lázaro Roberto ; Gómez Pérez, Jose Alberto ; Valle Garay, Aisel ; Blanco Santana, Rancés</creatorcontrib><description>Regulatory agencies establish that a broad physicochemical and biological characterization is necessary for the evaluation of comparability between a biosimilar candidate product and a reference commercial drug. Between them, conformational characterization of proteins is of vital importance to determine its folding and biological functions. In this work, the conformational features of a novel monoclonal antibody (called 5G4) were evaluated by means of circular dichroism spectroscopy and fluorescence. Secondary structure and thermal stability of mAbs were determined by circular dichroism in the far ultraviolet, while three-dimensional folding of proteins was analyzed by both circular dichroism in the near ultraviolet and intrinsic tryptophan fluorescence. In all experiments, Herceptin (Roche) was used as control. Both antibodies showed a composition of secondary structure predominantly of β-sheets (55-56%) and thermal stability of ~ 75°C, suggesting structural similarity. The three-dimensional folding of proteins was also similar due to the absorption spectra of the aromatic residues and the emission wavelength maxima by fluorescence were comparable. The values of the fluorescence attenuation constant (Stern-Volmer constant) for increasing concentrations of acrylamide were also similar, suggesting a degree of exposure of tryptophan residues similar, although it was slightly decreased for Herceptin. Our data permit to consider that 5G4 monoclonal antibody showed similar conformational characteristics when compared with Herceptin.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0215442</identifier><identifier>PMID: 31071101</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Absorption spectra ; Acrylamide ; Amides ; Analysis ; Animals ; Antibodies ; Antibodies, Monoclonal - chemistry ; Antibodies, Monoclonal - isolation & purification ; Antibodies, Monoclonal - pharmacology ; Attenuation ; Backup software ; Biochemistry ; Biological products ; Biology and Life Sciences ; Breast cancer ; Care and treatment ; CHO Cells ; Chromatography ; Chromatography, Gel ; Circular Dichroism ; Comparative analysis ; Cricetulus ; Dichroism ; Dimensional stability ; ErbB-2 protein ; Fluorescence ; Folding ; Growth factors ; Immunoglobulins ; Immunology ; Independent regulatory commissions ; Medicine and Health Sciences ; Models, Molecular ; Monoclonal antibodies ; Novels ; Patient outcomes ; Physical Sciences ; Protein Conformation ; Protein Folding ; Protein structure ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proteins ; Receptor, ErbB-2 - chemistry ; Receptor, ErbB-2 - metabolism ; Regulatory agencies ; Research and Analysis Methods ; Residues ; Secondary structure ; Spectrometry, Fluorescence ; Spectroscopy ; Structural stability ; Thermal stability ; Trastuzumab ; Trastuzumab - chemistry ; Trastuzumab - pharmacology ; Tryptophan ; Women's health</subject><ispartof>PloS one, 2019-05, Vol.14 (5), p.e0215442-e0215442</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Moro Pérez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Moro Pérez et al 2019 Moro Pérez et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-65e698f519693608b491823ecc9c4716e38ab4a59e528a2322dc9197fe16d3b33</citedby><cites>FETCH-LOGICAL-c692t-65e698f519693608b491823ecc9c4716e38ab4a59e528a2322dc9197fe16d3b33</cites><orcidid>0000-0002-2669-8131 ; 0000-0001-6947-1087</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508720/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508720/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31071101$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moro Pérez, Leina</creatorcontrib><creatorcontrib>Rodríguez Taño, Azalia de la Caridad</creatorcontrib><creatorcontrib>Martín Márquez, Lázaro Roberto</creatorcontrib><creatorcontrib>Gómez Pérez, Jose Alberto</creatorcontrib><creatorcontrib>Valle Garay, Aisel</creatorcontrib><creatorcontrib>Blanco Santana, Rancés</creatorcontrib><title>Conformational characterization of a novel anti-HER2 candidate antibody</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Regulatory agencies establish that a broad physicochemical and biological characterization is necessary for the evaluation of comparability between a biosimilar candidate product and a reference commercial drug. Between them, conformational characterization of proteins is of vital importance to determine its folding and biological functions. In this work, the conformational features of a novel monoclonal antibody (called 5G4) were evaluated by means of circular dichroism spectroscopy and fluorescence. Secondary structure and thermal stability of mAbs were determined by circular dichroism in the far ultraviolet, while three-dimensional folding of proteins was analyzed by both circular dichroism in the near ultraviolet and intrinsic tryptophan fluorescence. In all experiments, Herceptin (Roche) was used as control. Both antibodies showed a composition of secondary structure predominantly of β-sheets (55-56%) and thermal stability of ~ 75°C, suggesting structural similarity. The three-dimensional folding of proteins was also similar due to the absorption spectra of the aromatic residues and the emission wavelength maxima by fluorescence were comparable. The values of the fluorescence attenuation constant (Stern-Volmer constant) for increasing concentrations of acrylamide were also similar, suggesting a degree of exposure of tryptophan residues similar, although it was slightly decreased for Herceptin. Our data permit to consider that 5G4 monoclonal antibody showed similar conformational characteristics when compared with Herceptin.</description><subject>Absorption spectra</subject><subject>Acrylamide</subject><subject>Amides</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibodies, Monoclonal - isolation & purification</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Attenuation</subject><subject>Backup software</subject><subject>Biochemistry</subject><subject>Biological products</subject><subject>Biology and Life Sciences</subject><subject>Breast cancer</subject><subject>Care and treatment</subject><subject>CHO Cells</subject><subject>Chromatography</subject><subject>Chromatography, Gel</subject><subject>Circular Dichroism</subject><subject>Comparative analysis</subject><subject>Cricetulus</subject><subject>Dichroism</subject><subject>Dimensional stability</subject><subject>ErbB-2 protein</subject><subject>Fluorescence</subject><subject>Folding</subject><subject>Growth factors</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Independent regulatory commissions</subject><subject>Medicine and Health Sciences</subject><subject>Models, Molecular</subject><subject>Monoclonal antibodies</subject><subject>Novels</subject><subject>Patient outcomes</subject><subject>Physical Sciences</subject><subject>Protein Conformation</subject><subject>Protein Folding</subject><subject>Protein structure</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins</subject><subject>Receptor, ErbB-2 - chemistry</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Regulatory agencies</subject><subject>Research and Analysis Methods</subject><subject>Residues</subject><subject>Secondary structure</subject><subject>Spectrometry, Fluorescence</subject><subject>Spectroscopy</subject><subject>Structural stability</subject><subject>Thermal stability</subject><subject>Trastuzumab</subject><subject>Trastuzumab - chemistry</subject><subject>Trastuzumab - pharmacology</subject><subject>Tryptophan</subject><subject>Women's health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1r2zAUhs3YWLts_2BshsHYLpLpy7J0MyihawOFQvdxK05kOVFwrFSSy7pfPzlxSzx6Mctgc_Sc9-gcvVn2FqMZpiX-snGdb6GZ7VxrZojggjHyLDvFkpIpJ4g-P_o_yV6FsEGooILzl9kJxajEGOHT7GLu2tr5LUTrklqu1-BBR-Ptn30od3UOeevuTJNDG-308vyG5BraylYQzT62dNX96-xFDU0wb4bvJPv57fzH_HJ6dX2xmJ9dTTWXJE55YbgUdYEll5QjsWQSC0KN1lKzEnNDBSwZFNIURAChhFRaYlnWBvOKLimdZO8PurvGBTXMICiSHi7SWyRicSAqBxu183YL_l45sGofcH6lwEerG6MIYpgYSimTiKGaQyqRDiiIllDVUCetr0O1brk1lTZt9NCMRMc7rV2rlbtTvECiTIOfZJ8GAe9uOxOi2tqgTdNAa1zXn5tiybDAfWcf_kGf7m6gVpAasOnuUl3di6qzQjBJRFmyRM2eoNKqzNbqZJjapvgo4fMoITHR_I4r6EJQi-83_89e_xqzH4_YtYEmroNrut5aYQyyA6i9C8Gb-nHIGKne7w_TUL3f1eD3lPbu-IIekx4MTv8Cfkn4mg</recordid><startdate>20190509</startdate><enddate>20190509</enddate><creator>Moro Pérez, Leina</creator><creator>Rodríguez Taño, Azalia de la Caridad</creator><creator>Martín Márquez, Lázaro Roberto</creator><creator>Gómez Pérez, Jose Alberto</creator><creator>Valle Garay, Aisel</creator><creator>Blanco Santana, Rancés</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</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>ARAPS</scope><scope>ATCPS</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-2669-8131</orcidid><orcidid>https://orcid.org/0000-0001-6947-1087</orcidid></search><sort><creationdate>20190509</creationdate><title>Conformational characterization of a novel anti-HER2 candidate antibody</title><author>Moro Pérez, Leina ; Rodríguez Taño, Azalia de la Caridad ; Martín Márquez, Lázaro Roberto ; Gómez Pérez, Jose Alberto ; Valle Garay, Aisel ; Blanco Santana, Rancés</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-65e698f519693608b491823ecc9c4716e38ab4a59e528a2322dc9197fe16d3b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Absorption spectra</topic><topic>Acrylamide</topic><topic>Amides</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antibodies, Monoclonal - isolation & purification</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Attenuation</topic><topic>Backup software</topic><topic>Biochemistry</topic><topic>Biological products</topic><topic>Biology and Life Sciences</topic><topic>Breast cancer</topic><topic>Care and treatment</topic><topic>CHO Cells</topic><topic>Chromatography</topic><topic>Chromatography, Gel</topic><topic>Circular Dichroism</topic><topic>Comparative analysis</topic><topic>Cricetulus</topic><topic>Dichroism</topic><topic>Dimensional stability</topic><topic>ErbB-2 protein</topic><topic>Fluorescence</topic><topic>Folding</topic><topic>Growth factors</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Independent regulatory commissions</topic><topic>Medicine and Health Sciences</topic><topic>Models, Molecular</topic><topic>Monoclonal antibodies</topic><topic>Novels</topic><topic>Patient outcomes</topic><topic>Physical Sciences</topic><topic>Protein Conformation</topic><topic>Protein Folding</topic><topic>Protein structure</topic><topic>Protein Structure, Secondary</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins</topic><topic>Receptor, ErbB-2 - chemistry</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Regulatory agencies</topic><topic>Research and Analysis Methods</topic><topic>Residues</topic><topic>Secondary structure</topic><topic>Spectrometry, Fluorescence</topic><topic>Spectroscopy</topic><topic>Structural stability</topic><topic>Thermal stability</topic><topic>Trastuzumab</topic><topic>Trastuzumab - chemistry</topic><topic>Trastuzumab - pharmacology</topic><topic>Tryptophan</topic><topic>Women's health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moro Pérez, Leina</creatorcontrib><creatorcontrib>Rodríguez Taño, Azalia de la Caridad</creatorcontrib><creatorcontrib>Martín Márquez, Lázaro Roberto</creatorcontrib><creatorcontrib>Gómez Pérez, Jose Alberto</creatorcontrib><creatorcontrib>Valle Garay, Aisel</creatorcontrib><creatorcontrib>Blanco Santana, Rancés</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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 Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>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 Korea</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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moro Pérez, Leina</au><au>Rodríguez Taño, Azalia de la Caridad</au><au>Martín Márquez, Lázaro Roberto</au><au>Gómez Pérez, Jose Alberto</au><au>Valle Garay, Aisel</au><au>Blanco Santana, Rancés</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Conformational characterization of a novel anti-HER2 candidate antibody</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-05-09</date><risdate>2019</risdate><volume>14</volume><issue>5</issue><spage>e0215442</spage><epage>e0215442</epage><pages>e0215442-e0215442</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Regulatory agencies establish that a broad physicochemical and biological characterization is necessary for the evaluation of comparability between a biosimilar candidate product and a reference commercial drug. Between them, conformational characterization of proteins is of vital importance to determine its folding and biological functions. In this work, the conformational features of a novel monoclonal antibody (called 5G4) were evaluated by means of circular dichroism spectroscopy and fluorescence. Secondary structure and thermal stability of mAbs were determined by circular dichroism in the far ultraviolet, while three-dimensional folding of proteins was analyzed by both circular dichroism in the near ultraviolet and intrinsic tryptophan fluorescence. In all experiments, Herceptin (Roche) was used as control. Both antibodies showed a composition of secondary structure predominantly of β-sheets (55-56%) and thermal stability of ~ 75°C, suggesting structural similarity. The three-dimensional folding of proteins was also similar due to the absorption spectra of the aromatic residues and the emission wavelength maxima by fluorescence were comparable. The values of the fluorescence attenuation constant (Stern-Volmer constant) for increasing concentrations of acrylamide were also similar, suggesting a degree of exposure of tryptophan residues similar, although it was slightly decreased for Herceptin. Our data permit to consider that 5G4 monoclonal antibody showed similar conformational characteristics when compared with Herceptin.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31071101</pmid><doi>10.1371/journal.pone.0215442</doi><tpages>e0215442</tpages><orcidid>https://orcid.org/0000-0002-2669-8131</orcidid><orcidid>https://orcid.org/0000-0001-6947-1087</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-05, Vol.14 (5), p.e0215442-e0215442 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2222682685 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Absorption spectra Acrylamide Amides Analysis Animals Antibodies Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - isolation & purification Antibodies, Monoclonal - pharmacology Attenuation Backup software Biochemistry Biological products Biology and Life Sciences Breast cancer Care and treatment CHO Cells Chromatography Chromatography, Gel Circular Dichroism Comparative analysis Cricetulus Dichroism Dimensional stability ErbB-2 protein Fluorescence Folding Growth factors Immunoglobulins Immunology Independent regulatory commissions Medicine and Health Sciences Models, Molecular Monoclonal antibodies Novels Patient outcomes Physical Sciences Protein Conformation Protein Folding Protein structure Protein Structure, Secondary Protein Structure, Tertiary Proteins Receptor, ErbB-2 - chemistry Receptor, ErbB-2 - metabolism Regulatory agencies Research and Analysis Methods Residues Secondary structure Spectrometry, Fluorescence Spectroscopy Structural stability Thermal stability Trastuzumab Trastuzumab - chemistry Trastuzumab - pharmacology Tryptophan Women's health |
| title | Conformational characterization of a novel anti-HER2 candidate antibody |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T06%3A11%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Conformational%20characterization%20of%20a%20novel%20anti-HER2%20candidate%20antibody&rft.jtitle=PloS%20one&rft.au=Moro%20P%C3%A9rez,%20Leina&rft.date=2019-05-09&rft.volume=14&rft.issue=5&rft.spage=e0215442&rft.epage=e0215442&rft.pages=e0215442-e0215442&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0215442&rft_dat=%3Cgale_plos_%3EA584928774%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2222682685&rft_id=info:pmid/31071101&rft_galeid=A584928774&rft_doaj_id=oai_doaj_org_article_20412e33349040f6ad3b5e682c9adfaf&rfr_iscdi=true |