A mitochondria targeted nitroreductase-sensitive self-immolative spacer as an efficient shuttle for uncharged amine-based molecules.

ABSTRACT: Mitochondria have emerged as critical therapeutic targets in a wide range of diseases. The detailed examination of this organelle, as well as the search for methods to efficiently address it, therefore, represent significant challenges. In this article, we present a simple and robust method for the functionalization of uncharged amine-based molecules to enable their intracellular transport and selective accumulation in mitochondria. To this end, we have synthesized a self-immolative spacer that is both sensitive to mitochondrial nitroreductase and incorporates a triphenylphosphonium vectorising moiety. To demonstrate the efficacy of this mitochondrial shuttling technology, we have designed, synthesized, and employed a fluorogenic probe that unambiguously validates the concept. An initial e

SUBMITTER: Michel L 

PROVIDER: S-EPMC12422130 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature