Engineering protein-based therapeutics through structural and chemical design
Abstract Protein-based therapeutics have led to new paradigms in disease treatment. Projected to be half of the top ten selling drugs in 2023, proteins have emerged as rivaling and, in some cases, superior alternatives to historically used small molecule-based medicines. This review chronicles both...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38039-x |
| _version_ | 1797836330415161344 |
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| author | Sasha B. Ebrahimi Devleena Samanta |
| author_facet | Sasha B. Ebrahimi Devleena Samanta |
| author_sort | Sasha B. Ebrahimi |
| collection | DOAJ |
| description | Abstract Protein-based therapeutics have led to new paradigms in disease treatment. Projected to be half of the top ten selling drugs in 2023, proteins have emerged as rivaling and, in some cases, superior alternatives to historically used small molecule-based medicines. This review chronicles both well-established and emerging design strategies that have enabled this paradigm shift by transforming protein-based structures that are often prone to denaturation, degradation, and aggregation in vitro and in vivo into highly effective therapeutics. In particular, we discuss strategies for creating structures with increased affinity and targetability, enhanced in vivo stability and pharmacokinetics, improved cell permeability, and reduced amounts of undesired immunogenicity. |
| first_indexed | 2024-04-09T15:08:12Z |
| format | Article |
| id | doaj.art-1d6a307e66504e2fa9508dacdfbe4bb3 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T15:08:12Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-1d6a307e66504e2fa9508dacdfbe4bb32023-04-30T11:21:28ZengNature PortfolioNature Communications2041-17232023-04-0114111110.1038/s41467-023-38039-xEngineering protein-based therapeutics through structural and chemical designSasha B. Ebrahimi0Devleena Samanta1Drug Product Development—Steriles, GlaxoSmithKlineDepartment of Chemistry, The University of Texas at AustinAbstract Protein-based therapeutics have led to new paradigms in disease treatment. Projected to be half of the top ten selling drugs in 2023, proteins have emerged as rivaling and, in some cases, superior alternatives to historically used small molecule-based medicines. This review chronicles both well-established and emerging design strategies that have enabled this paradigm shift by transforming protein-based structures that are often prone to denaturation, degradation, and aggregation in vitro and in vivo into highly effective therapeutics. In particular, we discuss strategies for creating structures with increased affinity and targetability, enhanced in vivo stability and pharmacokinetics, improved cell permeability, and reduced amounts of undesired immunogenicity.https://doi.org/10.1038/s41467-023-38039-x |
| spellingShingle | Sasha B. Ebrahimi Devleena Samanta Engineering protein-based therapeutics through structural and chemical design Nature Communications |
| title | Engineering protein-based therapeutics through structural and chemical design |
| title_full | Engineering protein-based therapeutics through structural and chemical design |
| title_fullStr | Engineering protein-based therapeutics through structural and chemical design |
| title_full_unstemmed | Engineering protein-based therapeutics through structural and chemical design |
| title_short | Engineering protein-based therapeutics through structural and chemical design |
| title_sort | engineering protein based therapeutics through structural and chemical design |
| url | https://doi.org/10.1038/s41467-023-38039-x |
| work_keys_str_mv | AT sashabebrahimi engineeringproteinbasedtherapeuticsthroughstructuralandchemicaldesign AT devleenasamanta engineeringproteinbasedtherapeuticsthroughstructuralandchemicaldesign |