Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor.

ABSTRACT: HIV protease (PR) is required for proteolytic maturation in the late phase of HIV replication and represents a prime therapeutic target. The regulation and kinetics of viral polyprotein processing and maturation are currently not understood in detail. Here we design, synthesize, validate and apply a potent, photodegradable HIV PR inhibitor to achieve synchronized induction of proteolysis. The compound exhibits subnanomolar inhibition in vitro. Its photolabile moiety is released on light irradiation, reducing the inhibitory potential by 4 orders of magnitude. We determine the structure of the PR-inhibitor complex, analyze its photolytic products, and show that the enzymatic activity of inhibited PR can be fully restored on inhibitor photolysis. We also demonstrate that proteolysis of immatu

SUBMITTER: Schimer J 

PROVIDER: S-EPMC4366505 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature