A traceless linker for aliphatic amines that rapidly and quantitatively fragments after reduction.

ABSTRACT: Reduction sensitive linkers (RSLs) have the potential to transform the field of drug delivery due to their ease of use and selective cleavage in intracellular environments. However, despite their compelling attributes, developing reduction sensitive self-immolative linkers for aliphatic amines has been challenging due to their poor leaving group ability and high pK _a values. Here a traceless self-immolative linker composed of a dithiol-ethyl carbonate connected to a benzyl carbamate (DEC) is presented, which can modify aliphatic amines and release them rapidly and quantitatively after disulfide reduction. DEC was able to reversibly modify the lysine residues on CRISPR-Cas9 with either PEG, the cell penetrating peptide Arg₁₀, or donor DNA, and generated Cas9 con

SUBMITTER: He M 

PROVIDER: S-EPMC8163433 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature