Ranking mAb–excipient interactions in biologics formulations by NMR spectroscopy and computational approaches
Excipients are added to biopharmaceutical formulations to enhance protein stability and enable the development of robust formulations with acceptable physicochemical properties, but the mechanism by which they confer stability is not fully understood. Here, we aimed to elucidate the mechanism throug...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | mAbs |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2023.2212416 |
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| _version_ | 1849303987683065856 |
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| author | Chunting Zhang Steven T. Gossert Jonathan Williams Michael Little Marilia Barros Barton Dear Bradley Falk Ankit D. Kanthe Robert Garmise Luciano Mueller Andrew Ilott Anuji Abraham |
| author_facet | Chunting Zhang Steven T. Gossert Jonathan Williams Michael Little Marilia Barros Barton Dear Bradley Falk Ankit D. Kanthe Robert Garmise Luciano Mueller Andrew Ilott Anuji Abraham |
| author_sort | Chunting Zhang |
| collection | DOAJ |
| description | Excipients are added to biopharmaceutical formulations to enhance protein stability and enable the development of robust formulations with acceptable physicochemical properties, but the mechanism by which they confer stability is not fully understood. Here, we aimed to elucidate the mechanism through direct experimental evidence of the binding affinity of an excipient to a monoclonal antibody (mAb), using saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopic method. We ranked a series of excipients with respect to their dissociation constant (KD) and nonspecific binding constants (Ns). In parallel, molecular dynamic and site identification by ligand competitive saturation (SILCS)-Monte Carlo simulations were done to rank the excipient proximity to the proteins, thereby corroborating the ranking by STD NMR. Finally, the excipient ranking by NMR was correlated with mAb conformational and colloidal stability. Our approach can aid excipient selection in biologic formulations by providing insights into mAb–excipient affinities before conventional and time-consuming excipient screening studies are conducted. |
| format | Article |
| id | doaj-art-d07fb9b5f85d4dc88d56aaec9a92f83e |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-d07fb9b5f85d4dc88d56aaec9a92f83e2025-08-20T03:55:53ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2023.2212416Ranking mAb–excipient interactions in biologics formulations by NMR spectroscopy and computational approachesChunting Zhang0Steven T. Gossert1Jonathan Williams2Michael Little3Marilia Barros4Barton Dear5Bradley Falk6Ankit D. Kanthe7Robert Garmise8Luciano Mueller9Andrew Ilott10Anuji Abraham11Drug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USADrug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USADrug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USADrug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USADrug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USADrug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USADrug Discovery, Bristol Myers Squibb, Lawrenceville, NJ, USADrug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USADrug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USADrug Discovery, Bristol Myers Squibb, Lawrenceville, NJ, USADrug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USADrug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USAExcipients are added to biopharmaceutical formulations to enhance protein stability and enable the development of robust formulations with acceptable physicochemical properties, but the mechanism by which they confer stability is not fully understood. Here, we aimed to elucidate the mechanism through direct experimental evidence of the binding affinity of an excipient to a monoclonal antibody (mAb), using saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopic method. We ranked a series of excipients with respect to their dissociation constant (KD) and nonspecific binding constants (Ns). In parallel, molecular dynamic and site identification by ligand competitive saturation (SILCS)-Monte Carlo simulations were done to rank the excipient proximity to the proteins, thereby corroborating the ranking by STD NMR. Finally, the excipient ranking by NMR was correlated with mAb conformational and colloidal stability. Our approach can aid excipient selection in biologic formulations by providing insights into mAb–excipient affinities before conventional and time-consuming excipient screening studies are conducted.https://www.tandfonline.com/doi/10.1080/19420862.2023.2212416Excipient rankingmab stabilitymab–excipient interactionmolecular dynamicsMonte carloSTD NMR |
| spellingShingle | Chunting Zhang Steven T. Gossert Jonathan Williams Michael Little Marilia Barros Barton Dear Bradley Falk Ankit D. Kanthe Robert Garmise Luciano Mueller Andrew Ilott Anuji Abraham Ranking mAb–excipient interactions in biologics formulations by NMR spectroscopy and computational approaches mAbs Excipient ranking mab stability mab–excipient interaction molecular dynamics Monte carlo STD NMR |
| title | Ranking mAb–excipient interactions in biologics formulations by NMR spectroscopy and computational approaches |
| title_full | Ranking mAb–excipient interactions in biologics formulations by NMR spectroscopy and computational approaches |
| title_fullStr | Ranking mAb–excipient interactions in biologics formulations by NMR spectroscopy and computational approaches |
| title_full_unstemmed | Ranking mAb–excipient interactions in biologics formulations by NMR spectroscopy and computational approaches |
| title_short | Ranking mAb–excipient interactions in biologics formulations by NMR spectroscopy and computational approaches |
| title_sort | ranking mab excipient interactions in biologics formulations by nmr spectroscopy and computational approaches |
| topic | Excipient ranking mab stability mab–excipient interaction molecular dynamics Monte carlo STD NMR |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2023.2212416 |
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