Yeast Display Enables Identification of Covalent Single-Domain Antibodies against Botulinum Neurotoxin Light Chain A
| Autor: | Rafael Alcala-Torano, Mariha Islam, Jaclyn Cika, Kwok Ho Lam, Rongsheng Jin, Konstantin Ichtchenko, Charles B. Shoemaker, James A. Van Deventer |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | ACS Chemical Biology. 17:3435-3449 |
| ISSN: | 1554-8937 1554-8929 |
| DOI: | 10.1021/acschembio.2c00574 |
| Popis: | While covalent drug discovery is reemerging as an important route to small-molecule therapeutic leads, strategies for the discovery and engineering of protein-based irreversible binding agents remain limited. Here, we describe the use of yeast display in combination with noncanonical amino acids (ncAAs) to identify irreversible variants of single-domain antibodies (sdAbs), also called VHHs and nanobodies, targeting botulinum neurotoxin light chain A (LC/A). Starting from a series of previously described, structurally characterized sdAbs, we evaluated the properties of antibodies substituted with reactive ncAAs capable of forming covalent bonds with nearby groups after UV irradiation (when using 4-azido-l-phenylalanine) or spontaneously (when using |
| Databáze: | OpenAIRE |
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