Beyond 20 in the 21st Century: Prospects and Challenges of Non-canonical Amino Acids in Peptide Drug Discovery.
| Autor: | Hickey JL; Department of Medicinal Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States., Sindhikara D; Department of Modeling and Informatics, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States., Zultanski SL; Department of Process Research & Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States., Schultz DM; Department of Process Research & Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States. |
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| Jazyk: | angličtina |
| Zdroj: | ACS medicinal chemistry letters [ACS Med Chem Lett] 2023 Apr 24; Vol. 14 (5), pp. 557-565. Date of Electronic Publication: 2023 Apr 24 (Print Publication: 2023). |
| DOI: | 10.1021/acsmedchemlett.3c00037 |
| Abstrakt: | Life is constructed primarily using a toolbox of 20 canonical amino acids-relying upon these building blocks for the assembly of proteins and peptides that regulate nearly every cellular task, including cell structure, function, and maintenance. While Nature continues to be a source of inspiration for drug discovery, medicinal chemists are not beholden to only 20 canonical amino acids and have begun to explore non-canonical amino acids (ncAAs) for the construction of designer peptides with improved drug-like properties. However, as our toolbox of ncAAs expands, drug hunters are encountering new challenges in approaching the iterative peptide design-make-test-analyze cycle with a seemingly boundless set of building blocks. This Microperspective focuses on new technologies that are accelerating ncAA interrogation in peptide drug discovery (including HELM notation, late-stage functionalization, and biocatalysis) while shedding light on areas where further investment could not only accelerate the discovery of new medicines but also improve downstream development. Competing Interests: The authors declare no competing financial interest. (© 2023 American Chemical Society.) |
| Databáze: | MEDLINE |
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