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Bioorthogonal Self-Immolative Linker Based on Grob Fragmentation.

ABSTRACT: A self-immolative bioorthogonal conditionally cleavable linker based on Grob fragmentation is described. It is derived from 1,3-aminocyclohexanols and allows the release of sulfonate-containing compounds in aqueous media. Modulation of the amine pK_a promotes fragmentation even at slightly acidic pH, a common feature of several tumor environments. The Grob fragmentation can also occur under physiological conditions in living cells, highlighting the potential bioorthogonal applicability of this reaction.

SUBMITTER: Ferhati X

PROVIDER: S-EPMC8576835 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Bioorthogonal Self-Immolative Linker Based on Grob Fragmentation.

Ferhati Xhenti X Salas-Cubero Marina M Garrido Pablo P García-Sanmartín Josune J Guerreiro Ana A Avenoza Alberto A Busto Jesús H JH Peregrina Jesús M JM Martínez Alfredo A Jiménez-Moreno Ester E Bernardes Gonçalo J L GJL Corzana Francisco F

Organic letters 20211025 21

A self-immolative bioorthogonal conditionally cleavable linker based on Grob fragmentation is described. It is derived from 1,3-aminocyclohexanols and allows the release of sulfonate-containing compounds in aqueous media. Modulation of the amine pKa promotes fragmentation even at slightly acidic pH, a common feature of several tumor environments. The Grob fragmentation can also occur under physiological conditions in living cells, highlighting the potential bioorthogonal applic ...[more]

PMID: 34694118

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