New bioorthogonal self-immolative linker based on the Grob fragmentation reaction
- Xhenti Ferhati 1
- Pablo Garrido 2
- Josune García-Sanmartín 2
- Ana Guerreiro 3
- Alberto Avenoza 1
- J. Héctor Busto 1
- Jesús M. Peregrina 1
- Alfredo Martínez 2
- Ester Jiménez-Moreno 1
- Gonçalo J.L. Bernardes 34
- Francisco Corzana 1
- M. Salas-Cubero 1
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1
Universidad de La Rioja
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2
Centro de Investigación Biomédica de La Rioja
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3
Universidade de Lisboa
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4
University of Cambridge
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Editorial: Universidad de Granada
Año de publicación: 2022
Páginas: 140
Congreso: XXVIII Reunión Bienal GEQOR (Grupo Especializado de Química Orgánica). Granada 1 de julio de 2022
Tipo: Aportación congreso
beta Ver similares en nube de resultadosResumen
We have designed and synthesized a new self-immolative bioorthogonal cleavable linkerbased on the Grob fragmentation reaction that allows the controlled release of sulfonate-containing compounds such as a dansyl group under physiological conditions. We have alsotuned conveniently the pKa of the pushing group (amino group) using different substituents,leading to more efficient conversions at physiological pH and in some cases even at acidicpH, which is normally found in tumour environments. In addition, the Grob fragmentationtakes place under physiological conditions in living cells, demonstrating the potentialbioorthogonal applicability of the reaction. Based on these promising results, research iscurrently underway to incorporate this type of linker into antibody−drug conjugates for thetargeted delivery of cytotoxic drugs and fluorophores