HIV anti-latency treatment mediated by macromolecular prodrugs of histone deacetylase inhibitor, panobinostat.

ABSTRACT: Histone deacetylase inhibitors (HDACi) and panobinostat in particular are currently in the focus of intensive investigation as latency reversing agents against the human immunodeficiency virus (HIV). Regretfully, HDACi have dose limiting side-effects making controlled, optimized methods for delivery of panobinostat highly warranted. This has proven to be highly challenging, predominantly because panobinostat has no readily available classic sites for bioconjugation. In this work, we address this challenge and present the first macromolecular prodrugs of panobinostat engineered using self immolative linkers (SIL) and a disulfide trigger for drug release upon cell entry. Synthetic methodology involved the development of a novel monomer with functionalities of SIL and activated ester for one-

SUBMITTER: Zuwala K 

PROVIDER: S-EPMC6003675 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature