Defects in aryl hydrocarbon receptor interacting protein-like1 (AIPL1) are associated with blinding diseases with a wide range of severity in humans. We examined the mechanism behind autosomal dominant cone-rod dystrophy (adCORD) caused by 12 base pair (bp) deletion at proline 351 of hAIPL1 (P351Δ12) mutation in the primate-specific region of human AIPL1. Mutant P351Δ12 human isoform, aryl hydr...

In a previous cross-linking study we have shown that the cytosolic aryl hydrocarbon receptor (AhR) complex has a heterotetrameric structure (Perdew, G. H. (1992) Biochem. Biophys. Res. Commun. 182, 55-62). In this report, both cross-linked and [35S]methionine-labeled Hepa 1c1c7 cytosol were used to characterize the subunit composition of the AhR complex by immunoprecipitation with an AhR polycl...

A series of bulky geometry-constrained iminopyridylpalladium chlorides were developed. The steric environment adjacent to the nitrogen atom in the pyridine rings and diimine parts enhanced the thermal stability of the palladium species. Bulkier groups at the imino group stabilized the palladium species and the corresponding palladium chlorides showed high activities in the coupling reaction of ...

Novel syntheses of C-nucleoside analogs with aryl quinoxalines as nucleobase surrogates have been accomplished by mild and efficient three-component sequential reactions in high yields with a wide scope of substrates. The mechanism was clarified by isolation of novel sugar 1,2-diketone derived from oxidation of the corresponding alkyne.

An assay has been developed and measurements of aryl hydrocarbon [benzo(a)pyrene] hydroxylase have been made in peripheral blood monocytes from a human population. Treatment with benz(a)anthracene in cell culture increased aryl hydrocarbon hydroxylase activity from 6.5 to 37-fold in monocytes from each of 25 apparently healthy donors. A weak correlation (r = 0.38) was observed between the induc...

We describe the functionalization of α-amino C-H bonds with aryl halides using a combination of nickel and photoredox catalysis. This direct C-H, C-X coupling uses inexpensive and readily available starting materials to generate benzylic amines, an important class of bioactive molecules. Mechanistically, this method features the direct arylation of α-amino radicals mediated by a nickel catalyst...

The design of specific inhibitors against the Hsp90 chaperone and other enzyme relies on the detailed and correct understanding of both the thermodynamics of inhibitor binding and the structural features of the protein-inhibitor complex. Here we present a detailed thermodynamic study of binding of aryl-dihydroxyphenyl-thiadiazole inhibitor series to recombinant human Hsp90 alpha isozyme. The in...

From the biochemical point of view, the aryl hydrocarbon receptor (AHR) is a highly conserved, developmentally regulated, and ligand-activated member of the bHLH/PAS family of transcription factors. The AHR was originally discovered because of the human and animal toxicity of its most potent and persistent ligand, 2,3,7,8-tetrachlorodibenzo-pdioxin, usually just referred to as “dioxin.” The can...