Disulfide reshuffling triggers the release of a thiol-free anti-HIV agent to make up fast-acting, potent macromolecular prodrugs

Anders Kock; Kaja Zuwala; Anton A A Smith; Pau Ruiz-Sanchis; Benjamin M Wohl; Martin Tolstrup; Alexander N Zelikin

doi:10.1039/c4cc04280h

Disulfide reshuffling triggers the release of a thiol-free anti-HIV agent to make up fast-acting, potent macromolecular prodrugs

Chem Commun (Camb). 2014 Dec 4;50(93):14498-500. doi: 10.1039/c4cc04280h.

Authors

Anders Kock¹, Kaja Zuwala, Anton A A Smith, Pau Ruiz-Sanchis, Benjamin M Wohl, Martin Tolstrup, Alexander N Zelikin

Affiliation

¹ Department of Chemistry, Aarhus University, Aarhus, Denmark. [email protected].

PMID: 25285337
DOI: 10.1039/c4cc04280h

Abstract

The release of azidothymidine from macromolecular prodrugs was designed to respond to the intracellular disulfide reshuffling. This drug has no thiol groups, and a response to this trigger was engineered using a self-immolative linker. The resulting formulations were fast-acting, efficacious, and highly potent with regards to suppressing the infectivity of the virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacology*
Cell Line
Disulfides / chemistry*
Dose-Response Relationship, Drug
HIV Infections / drug therapy*
HIV-1 / drug effects*
Humans
Macromolecular Substances / chemistry
Macromolecular Substances / pharmacology
Microbial Sensitivity Tests
Molecular Structure
Prodrugs / chemistry*
Prodrugs / pharmacology*
Structure-Activity Relationship
Time Factors
Zidovudine / chemistry
Zidovudine / pharmacology*

Substances

Anti-HIV Agents
Disulfides
Macromolecular Substances
Prodrugs
Zidovudine