Design and synthesis of photoactivatable aryl diketo acid-containing HIV-1 integrase inhibitors as potential affinity probes

Xuechun Zhang; Christophe Marchand; Yves Pommier; Terrence R Burke Jr

doi:10.1016/j.bmcl.2003.12.064

Design and synthesis of photoactivatable aryl diketo acid-containing HIV-1 integrase inhibitors as potential affinity probes

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1205-7. doi: 10.1016/j.bmcl.2003.12.064.

Authors

Xuechun Zhang¹, Christophe Marchand, Yves Pommier, Terrence R Burke Jr

Affiliation

¹ Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI-Frederick, PO Box B, Bldg. 376 Boyles Street, Frederick, MD 21702-1201, USA.

PMID: 14980666
DOI: 10.1016/j.bmcl.2003.12.064

Abstract

Aryl diketo acids (ADKs) represent an important new class of HIV-1 integrase (IN) inhibitors. In order to facilitate examination of the structural basis underlying IN?ADK interaction, biphenyl ketone and phenyl azide photophores were incorporated into ADK structures. Of particular note is the novel dual utilization of azide and phenyketone moieties for both enzyme recognition and for crosslinking. The resulting analogues maintained low micromolar inhibitory potency against IN in recombinant in vitro assays. These potential HIV-1 integrase photoaffinity labels may provide useful tools for studying enzyme interactions of the ADK inhibitor class.

MeSH terms

Drug Design*
HIV Integrase / metabolism*
HIV Integrase Inhibitors / chemical synthesis*
HIV Integrase Inhibitors / pharmacology
Keto Acids / chemical synthesis
Keto Acids / pharmacology*
Light*

Substances

HIV Integrase Inhibitors
Keto Acids
HIV Integrase