58026-25-8Relevant articles and documents
Self-assembly of Fluorescent Dehydroberberine Enhances Mitochondria-Dependent Antitumor Efficacy
An, Ruibing,Gu, Zhanni,Sun, Haifeng,Hu, Yuxuan,Yan, Runqi,Ye, Deju,Liu, Hong
supporting information, p. 9812 - 9819 (2018/07/25)
Selective imaging and inducing mitochondrial dysfunction in tumor cells using mitochondria-targeting probes has become as a promising approach for cancer diagnosis and therapy. Here, we report the design of a fluorescent berberine analog, dehydroberberine (DH-BBR), as a new mitochondria-targeting probe capable of self-assembling into monodisperse organic nanoparticles (DTNPs) upon integration with a lipophilic counter anion, allowing for enhanced fluorescence imaging and treatment of tumors in living mice. X-ray crystallography revealed that the self-assembly process was attributed to a synergy of different molecular interactions, including π–π stacking, O???π interaction and electrostatic interaction between DH-BBR and counter anions. We demonstrated that DTNPs could efficiently enter tumor tissue following intravenous injection and enhance mitochondrial delivery of DH-BBR via an electrostatic interaction driven anion exchange process. Selective accumulation in the mitochondria capable of emitting strong fluorescence and causing mitochondrial dysfunction was achieved, enabling efficient inhibition of tumor growth in living mice. This study demonstrates promise for applying lipophilic anions to control molecular self-assembly and tune antitumor activity of mitochondria-targeting probes, which can facilitate to improve cancer treatment in vivo.
Mechanistic and structural analysis of Drosophila melanogaster arylalkylamine N-acetyltransferases
Dempsey, Daniel R.,Jeffries, Kristen A.,Bond, Jason D.,Carpenter, Anne-Marie,Rodriguez-Ospina, Santiago,Breydo, Leonid,Caswell, K. Kenneth,Merkler, David J.
, p. 7777 - 7793 (2015/02/19)
(Chemical Equation Presented). Arylalkylamine N-acetyltransferase (AANAT) catalyzes the penultimate step in the biosynthesis of melatonin and other N-acetylarylalkylamides from the corresponding arylalkylamine and acetyl-CoA. The N-acetylation of arylalkylamines is a critical step in Drosophila melanogaster for the inactivation of the bioactive amines and the sclerotization of the cuticle. Two AANAT variants (AANATA and AANATB) have been identified in D. melanogaster , in which AANATA differs from AANATB by the truncation of 35 amino acids from the N-terminus. We have expressed and purified both D. melanogaster AANAT variants (AANATA and AANATB) in Escherichia coli and used the purified enzymes to demonstrate that this N-terminal truncation does not affect the activity of the enzyme. Subsequent characterization of the kinetic and chemical mechanism of AANATA identified an ordered sequential mechanism, with acetyl-CoA binding first, followed by tyramine. We used a combination of pH-activity profiling and site-directed mutagenesis to study prospective residues believed to function in AANATA catalysis. These data led to an assignment of Glu-47 as the general base in catalysis with an apparent pKa of 7.0. Using the data generated for the kinetic mechanism, structure-function relationships, pH-rate profiles, and site-directed mutagenesis, we propose a chemical mechanism for AANATA.
The E.S.R. Spectra of Cation Radicals Derived from Phenethyltetrahydroisoquinoline Ethers and Model Compounds
Hewgill, Frank R.,Pass, Michael C.
, p. 555 - 563 (2007/10/02)
Cation radicals derived from the title compounds by oxidation with thallium tristrifluoroacetate have been characterized.The structures assigned to these radicals suggest that initial oxidation occures at the phenethyl ring in the compounds examined.Oxidation of homolaudanosine in this way gave the expected homoaporphine.
