Synthesis and biological study of a flavone acetic acid analogue containing an azido reporting group designed as a multifunctional binding site probe.
Flavone-8-acetic acid (FAA) is a potent immunomodulatory small molecule that is uniquely characterized as being active on mouse but not human cells. Although FAA is a potent inducer of murine cytokine, chemokine and interferon gene expression, its mode of action remains unknown. In this report, we describe the synthesis of a new flavone acetic acid (FAA) analogue, (2-[2-(4-azidophenyl)-4-oxochromen-8-yl-]acetic acid (compound 2). We demonstrate that compound 2 is equally active as the parent FAA in inducing chemokine gene expression and that the azide functional group is capable of reacting with a reporter molecule, such as the FLAG peptide-phosphine, under mild conditions. This reaction will be useful for detecting the drug-bound protein active complex utilizing an anti-FLAG antibody.
Malolanarasimhan
Krishnan
K
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute-Frederick, Center for Cancer Research, Frederick, MD 21702-1201, USA.
Lai
Christopher C
CC
Kelley
James A
JA
Iaccarino
Lynn
L
Reynolds
Della
D
Young
Howard A
HA
Marquez
Victor E
VE
D000818:Animals; D001386:Azides / Q000737:chemistry*; D001665:Binding Sites / Q000187:drug effects; D002460:Cell Line; D018925:Chemokines / Q000235:genetics; D015195:Drug Design; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry; D010720:Phosphines / Q000737:chemistry; D012313:RNA / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
D001386:Azides; D018925:Chemokines; D005419:Flavonoids; D009842:Oligopeptides; D010455:Peptides; D010720:Phosphines; D012313:RNA; C049328:flavone acetic acid; C085706:FLAG peptide; C044646:phosphine