New bioorthogonal self-immolative linker based on the Grob fragmentation reaction

  1. Xhenti Ferhati 1
  2. Pablo Garrido 2
  3. Josune García-Sanmartín 2
  4. Ana Guerreiro 3
  5. Alberto Avenoza 1
  6. J. Héctor Busto 1
  7. Jesús M. Peregrina 1
  8. Alfredo Martínez 2
  9. Ester Jiménez-Moreno 1
  10. Gonçalo J.L. Bernardes 34
  11. Francisco Corzana 1
  12. M. Salas-Cubero 1
  1. 1 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  2. 2 Centro de Investigación Biomédica de La Rioja
    info

    Centro de Investigación Biomédica de La Rioja

    Logroño, España

    ROR https://ror.org/03vfjzd38

  3. 3 Universidade de Lisboa
    info

    Universidade de Lisboa

    Lisboa, Portugal

    ROR https://ror.org/01c27hj86

  4. 4 University of Cambridge
    info

    University of Cambridge

    Cambridge, Reino Unido

    ROR https://ror.org/013meh722

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Proceedings:
XXVIII Reunión Bienal GEQOR (Grupo Especializado de Química Orgánica). Libro de abstracts

Publisher: Universidad de Granada

Year of publication: 2022

Pages: 140

Congress: XXVIII Reunión Bienal GEQOR (Grupo Especializado de Química Orgánica). Granada 1 de julio de 2022

Type: Conference paper

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Abstract

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