Morpholine-Facilitated Enrichment-Triggered Delivery of Carbon Monoxide to Lysosome: A Feasibility Study.

ABSTRACT: Targeted delivery of carbon monoxide (CO) prodrugs holds important therapeutic potential for various applications. Along this line, we developed an enrichment-triggered release (ETR) approach for activating 2-component (a diene and a dienophile) CO prodrugs upon enrichment in the mitochondrion, giving a "one stone, two birds" approach. Herein, we aim to broaden the scope of application to targeted delivery to the lysosome. We tethered a CO prodrug pair, a diene and a dienophile, with morpholine, a lysosomal targeting moiety. Several analogs were synthesized to tune the second-order rate constants (k₂) to a desirable range. We chose two pairs of the prodrugs with different second-order rate constants (0.087 and 0.21 M^-1 s^-1) to further study their enrichment

SUBMITTER: Tripathi R 

PROVIDER: S-EPMC12534755 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature