Feedback prodrug

摘要

Compounds and methods for use in selectively inhibiting a lytic enzyme based on feedback inhibition are described. The conjugated compound serves as a substrate for a lytic enzyme. Cleavage of the conjugated compound by the lytic enzyme releases an inhibitor of the enzyme.

主权项

1. A conjugated compound comprising:
a first constituent comprising an enzymatic substrate comprising a mannoside; and a second constituent covalently linked to the first constituent, the second constituent comprising a mannosidase inhibitor selected from the group consisting of mannostatin A, mannostatin B, or a mannostatin A derivative wherein the methyl thioether group (—S—CH3) group of mannostatin A is replaced by a phenyl thioether group (—S—Ph), a methoxy group (—O—CH3) or a phenoxy group (—O—Ph); and wherein the covalent linkage between the first and second constituents can be enzymatically cleaved by a mannosidase to release the mannosidase inhibitor; and wherein the mannosidase inhibitor, when released from the conjugated compound, inhibits the activity of the mannosidase.