Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro.

ABSTRACT: Bryostatin is a unique lead in the development of potentially transformative therapies for cancer, Alzheimer's disease and the eradication of HIV/AIDS. However, the clinical use of bryostatin has been hampered by its limited supply, difficulties in accessing clinically relevant derivatives, and side effects. Here, we address these problems through the step-economical syntheses of seven members of a new family of designed bryostatin analogues using a highly convergent Prins-macrocyclization strategy. We also demonstrate for the first time that such analogues effectively induce latent HIV activation in vitro with potencies similar to or better than bryostatin. Significantly, these analogues are up to 1,000-fold more potent in inducing latent HIV expression than prostratin, the current clinic

SUBMITTER: DeChristopher BA 

PROVIDER: S-EPMC3428736 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature