From Ugi Multicomponent Reaction to Linkers for Bioconjugation
| Autor: | Beatriz Somovilla-Crespo, Juan M. Zapata, Iván Ramos-Tomillero, Gema Perez-Chacon, Carmen Cuevas, Juan Manuel Domínguez, Hortensia Rodríguez, Fernando Albericio, Francisco Sánchez-Madrid |
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| Přispěvatelé: | Generalitat de Catalunya, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), National Research Foundation (South Africa), Universidad Yachay Tech |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname ACS Omega ACS Omega, Vol 5, Iss 13, Pp 7424-7431 (2020) |
| ISSN: | 2470-1343 |
| DOI: | 10.1021/acsomega.0c00099 |
| Popis: | Bioconjugation is a key approach for the development of novel molecular entities with clinical applications. The biocompatibility and specificity of biomolecules such as peptides, proteins, and antibodies make these macromolecules ideal carriers for selective targeted therapies. In this context, there is a need to develop new molecular units that cover the requirements of the next generation of targeted pharmaceuticals. Here, we present the design and development of a versatile and stable linker based on a N-alkylated α,α-dialkyl dipeptide for bioconjugation, with a particular focus on antibody-drug conjugates (ADCs). Starting with the well-known Ugi multicomponent reaction, the convenient chemical modification of the prepared adducts allowed us the obtention of versatile bifunctional linkers for bioconjugation. A conjugation strategy was tested to demonstrate the efficiency of the linker. In addition, a novel cytotoxic anti-HER2 ADC was prepared using the Ugi-linker approach. I.R-T. thanks the Generalitat de Catalunya for a predoctoral fellowship. This work was funded in part by the following: the Ministerio de Economía y Competitividad [Programa INNPACTO, project MarinMab (IPT-2012-0198-090000) and RTI2018-093831-B-100], the Generalitat de Catalunya (2017-SGR-1439), and the Institute for Research in Biomedicine Barcelona (IRB Barcelona) (Spain); National Research Foundation (Blue Skies, # 120386) (South Africa); and Yachay Tech (Ecuador). |
| Databáze: | OpenAIRE |
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