Characterization of binding between model protein GA-Z and human serum albumin using asymmetrical flow field-flow fractionation and small angle X-ray scattering
Protein-based drugs often require targeted drug delivery for optimal therapy. A successful strategy to increase the circulation time of the protein in the blood is to link the therapeutic protein with an albumin-binding domain. In this work, we characterized such a protein-based drug, GA-Z. Using as...
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| creator | Choi, Jaeyeong Wahlgren, Marie Ek, Vilhelm Elofsson, Ulla Fransson, Jonas Nilsson, Lars Terry, Ann Söderberg, Christopher A G |
| description | Protein-based drugs often require targeted drug delivery for optimal therapy. A successful strategy to increase the circulation time of the protein in the blood is to link the therapeutic protein with an albumin-binding domain. In this work, we characterized such a protein-based drug, GA-Z. Using asymmetrical flow field-flow fractionation coupled with multi-angle light scattering (AF4-MALS) we investigated the GA-Z monomer-dimer equilibrium as well as the molar binding ratio of GA-Z to HSA. Using small angle X-ray scattering, we studied the structure of GA-Z as well as the complex between GA-Z and HSA. The results show that GA-Z is predominantly dimeric in solution at pH 7 and that it binds to monomeric as well as dimeric HSA. Furthermore, GA-Z binds to HSA both as a monomer and a dimer, and thus, it can be expected to stay bound also upon dilution following injection in the blood stream. The results from SAXS and binding studies indicate that the GA-Z dimer is formed between two target domains (Z-domains). The results also indicate that the binding of GA-Z to HSA does not affect the ratio between HSA dimers and monomers, and that no higher order oligomers of the complex are seen other than those containing dimers of GA-Z and dimers of HSA. |
| doi_str_mv | 10.1371/journal.pone.0242605 |
| format | Article |
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A successful strategy to increase the circulation time of the protein in the blood is to link the therapeutic protein with an albumin-binding domain. In this work, we characterized such a protein-based drug, GA-Z. Using asymmetrical flow field-flow fractionation coupled with multi-angle light scattering (AF4-MALS) we investigated the GA-Z monomer-dimer equilibrium as well as the molar binding ratio of GA-Z to HSA. Using small angle X-ray scattering, we studied the structure of GA-Z as well as the complex between GA-Z and HSA. The results show that GA-Z is predominantly dimeric in solution at pH 7 and that it binds to monomeric as well as dimeric HSA. Furthermore, GA-Z binds to HSA both as a monomer and a dimer, and thus, it can be expected to stay bound also upon dilution following injection in the blood stream. The results from SAXS and binding studies indicate that the GA-Z dimer is formed between two target domains (Z-domains). The results also indicate that the binding of GA-Z to HSA does not affect the ratio between HSA dimers and monomers, and that no higher order oligomers of the complex are seen other than those containing dimers of GA-Z and dimers of HSA.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0242605</identifier><identifier>PMID: 33232370</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Albumin ; Analysis ; Asymmetry ; Binding ; Binding sites ; Biological products ; Biology and Life Sciences ; Blood ; Blood circulation ; Chemistry Techniques, Analytical - methods ; Chromatography ; Chromatography, Gel ; Crystal structure ; Crystallography ; Dilution ; Dimerization ; Dimers ; Drug delivery ; Drug delivery systems ; Drug dosages ; Earth Sciences ; Engineering ; Engineering and Technology ; Fatty acids ; Food science ; Fractionation ; Human serum albumin ; Humans ; Industrial Biotechnology ; Industriell bioteknik ; Light scattering ; Models, Molecular ; Molecular Weight ; Monomers ; Nutrition ; Oligomers ; Peptides ; Physical Sciences ; Protein Binding ; Protein Conformation ; Protein separation ; Proteins ; Recombinant Fusion Proteins - metabolism ; Research and Analysis Methods ; Scattering, Small Angle ; Serum albumin ; Serum Albumin, Human - metabolism ; Small angle X ray scattering ; Teknik ; X-ray scattering</subject><ispartof>PloS one, 2020-11, Vol.15 (11), p.e0242605</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Choi et al. 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A successful strategy to increase the circulation time of the protein in the blood is to link the therapeutic protein with an albumin-binding domain. In this work, we characterized such a protein-based drug, GA-Z. Using asymmetrical flow field-flow fractionation coupled with multi-angle light scattering (AF4-MALS) we investigated the GA-Z monomer-dimer equilibrium as well as the molar binding ratio of GA-Z to HSA. Using small angle X-ray scattering, we studied the structure of GA-Z as well as the complex between GA-Z and HSA. The results show that GA-Z is predominantly dimeric in solution at pH 7 and that it binds to monomeric as well as dimeric HSA. Furthermore, GA-Z binds to HSA both as a monomer and a dimer, and thus, it can be expected to stay bound also upon dilution following injection in the blood stream. The results from SAXS and binding studies indicate that the GA-Z dimer is formed between two target domains (Z-domains). 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metabolism</subject><subject>Research and Analysis Methods</subject><subject>Scattering, Small Angle</subject><subject>Serum albumin</subject><subject>Serum Albumin, Human - metabolism</subject><subject>Small angle X ray scattering</subject><subject>Teknik</subject><subject>X-ray scattering</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</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><sourceid>D8T</sourceid><sourceid>DOA</sourceid><recordid>eNqNk29r1TAUxosobk6_gWhBEEXuTJqkad8Il6lzMBj4Z4hvwmlyem9G2lyT1jk_jR_VdPdu7MoECaGH5HeekzzpybLHlOxTJunrMz-GHtz-yve4TwpelETcyXZpzYpZWRB290a8kz2I8YwQwaqyvJ_tMFakIclu9vtgCQH0gMH-gsH6Pvdt3tje2H6RNzicI_Z55w26fBX8gLbPD-ezbzn0Jl-OHfR5xDB2Obhm7NLmGKdEiBddh0OwGlzeOn-etxadma3DqV6qtC43CcUOnEvRwmH-dRbgIo8ahulM_eJhdq8FF_HR5ruXfXn_7vPBh9nxyeHRwfx4pmUth5mujeSFNEZwJgpGiJZtoYta15SwpmgLo6uSVk1dAatlgwZBlg3FqgTZGG7YXvZ0rbtyPqqNuVEVvORUSEFkIo7WhPFwplbBdhAulAerLhd8WCgIg9UOFSTnJTasSoV5gwiCQFlJXYA2zNA2aR2vteI5rsZmS82NqzSbNFVERQSh0rSlYpxwxSVUCnQtFOWaaSom6SrJvfqn3Ft7Or88XLBKkJqLRL_ZXHVsOjQa-yGA20ra3untUi38DyXLSnDJk8CLjUDw30eMg-ps1Ogc9OjHjWlVRUSd0Gd_obdbu6EWkNyzfetTXT2JqnmZnpVSwcpE7d9CpWGwszq1QWvT-lbCy62ExAz4c1jAGKM6-vTx_9mT0232-Q12ieCGZfRunH7ouA3yNaiDjzFge20yJWrq4is31NTFatPFKe3JzQe6TrpqW_YHeU1Eog</recordid><startdate>20201124</startdate><enddate>20201124</enddate><creator>Choi, Jaeyeong</creator><creator>Wahlgren, Marie</creator><creator>Ek, Vilhelm</creator><creator>Elofsson, Ulla</creator><creator>Fransson, Jonas</creator><creator>Nilsson, Lars</creator><creator>Terry, Ann</creator><creator>Söderberg, Christopher A G</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>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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><scope>AGCHP</scope><scope>D95</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0850-2676</orcidid></search><sort><creationdate>20201124</creationdate><title>Characterization of binding between model protein GA-Z and human serum albumin using asymmetrical flow field-flow fractionation and small angle X-ray scattering</title><author>Choi, Jaeyeong ; Wahlgren, Marie ; Ek, Vilhelm ; Elofsson, Ulla ; Fransson, Jonas ; Nilsson, Lars ; Terry, Ann ; Söderberg, Christopher A G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c797t-c9d7427dd54352300c7f2c29c9103b2f2dc8618b98a397bedea76b1e86a7bd4d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Albumin</topic><topic>Analysis</topic><topic>Asymmetry</topic><topic>Binding</topic><topic>Binding sites</topic><topic>Biological products</topic><topic>Biology and Life Sciences</topic><topic>Blood</topic><topic>Blood circulation</topic><topic>Chemistry Techniques, Analytical - 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A successful strategy to increase the circulation time of the protein in the blood is to link the therapeutic protein with an albumin-binding domain. In this work, we characterized such a protein-based drug, GA-Z. Using asymmetrical flow field-flow fractionation coupled with multi-angle light scattering (AF4-MALS) we investigated the GA-Z monomer-dimer equilibrium as well as the molar binding ratio of GA-Z to HSA. Using small angle X-ray scattering, we studied the structure of GA-Z as well as the complex between GA-Z and HSA. The results show that GA-Z is predominantly dimeric in solution at pH 7 and that it binds to monomeric as well as dimeric HSA. Furthermore, GA-Z binds to HSA both as a monomer and a dimer, and thus, it can be expected to stay bound also upon dilution following injection in the blood stream. The results from SAXS and binding studies indicate that the GA-Z dimer is formed between two target domains (Z-domains). The results also indicate that the binding of GA-Z to HSA does not affect the ratio between HSA dimers and monomers, and that no higher order oligomers of the complex are seen other than those containing dimers of GA-Z and dimers of HSA.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33232370</pmid><doi>10.1371/journal.pone.0242605</doi><tpages>e0242605</tpages><orcidid>https://orcid.org/0000-0002-0850-2676</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Albumin Analysis Asymmetry Binding Binding sites Biological products Biology and Life Sciences Blood Blood circulation Chemistry Techniques, Analytical - methods Chromatography Chromatography, Gel Crystal structure Crystallography Dilution Dimerization Dimers Drug delivery Drug delivery systems Drug dosages Earth Sciences Engineering Engineering and Technology Fatty acids Food science Fractionation Human serum albumin Humans Industrial Biotechnology Industriell bioteknik Light scattering Models, Molecular Molecular Weight Monomers Nutrition Oligomers Peptides Physical Sciences Protein Binding Protein Conformation Protein separation Proteins Recombinant Fusion Proteins - metabolism Research and Analysis Methods Scattering, Small Angle Serum albumin Serum Albumin, Human - metabolism Small angle X ray scattering Teknik X-ray scattering |
| title | Characterization of binding between model protein GA-Z and human serum albumin using asymmetrical flow field-flow fractionation and small angle X-ray scattering |
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