RESUMO
El síndrome de Eagle consiste en una elongación de los procesos estiloides con una calcificación de los ligamentos estilohioideos, uni o bilateral. Característicamente produce una cefalea de localización temporal o retroauricular, que se exacerba con el habla y la masticación, con dolor a la palpación de los pilares amigdalinos. Conocer su forma de presentación clínica y semiológica permite solicitar las pruebas complementarias adecuadas que eviten demoras en el diagnóstico y orientar así el tratamiento correcto.
Assuntos
Cefaleia , Humanos , Estudos RetrospectivosRESUMO
Eagle syndrome consists of an elongation of the styloid processes with calcification of the stylohyoid ligaments, unilaterally or bilaterally. Characteristically, it produces a temporal or retroauricular headache, which is exacerbated by speaking and chewing, with pain on palpation of the tonsillar pillars. Knowing its form of clinical and semiological presentation allows requesting the appropriate complementary tests that avoid delays in diagnosis and thus guide the correct treatment.
El síndrome de Eagle consiste en una elongación de los procesos estiloides con una calcificación de los ligamentos estilohioideos, uni o bilateral. Característicamente produce una cefalea de localización temporal o retroauricular, que se exacerba con el habla y la masticación, con dolor a la palpación de los pilares amigdalinos. Conocer su forma de presentación clínica y semiológica permite solicitar las pruebas complementarias adecuadas que eviten demoras en el diagnóstico y orientar así el tratamiento correcto.
Assuntos
Cefaleia , HumanosRESUMO
We present a chemical methylome analysis platform to evaluate the inhibitory activity of small molecules towards poorly characterized protein methyltransferases (PMTs), facsilitating to identify syn-HyPA-ETP-2 as a non-histone arginine methyltransferase inhibitor.
Assuntos
Dicetopiperazinas/farmacologia , Inibidores Enzimáticos/farmacologia , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Animais , Dicetopiperazinas/síntese química , Dicetopiperazinas/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Células HEK293 , Ribonucleoproteínas Nucleares Heterogêneas Grupo K , Humanos , Camundongos , Compostos Organosselênicos/química , Piperazinas/química , Ribonucleoproteínas/metabolismo , S-Adenosilmetionina/análogos & derivados , S-Adenosilmetionina/química , EstereoisomerismoRESUMO
Lysine methylation has been extensively studied in histones, where it has been shown to provide specific epigenetic marks for the regulation of gene expression; however, the molecular mechanism and physiological function of lysine methylation in proteins other than histones remains to be fully addressed. To better understand the substrate diversity of lysine methylation, S-adenosylmethionine (SAM) derivatives with alkyne-moieties have been synthesized. A selenium-based SAM analog, propargylic Se-adenosyl-l-selenomethionine (ProSeAM), has a wide spectrum of reactivity against various lysine methyltransferases (KMTs) with sufficient stability to support enzymatic reactions in vitro. By using ProSeAM as a chemical probe for lysine methylation, we identified substrates for two seven-beta-strand KMTs, METTL21A and METTL10, on a proteomic scale in mammalian cells. METTL21A has been characterized as a heat shock protein (HSP)-70 methyltransferase. Mammalian METTL10 remains functionally uncharacterized, although its ortholog in yeast, See1, has been shown to methylate the translation elongation factor eEF1A. By using ProSeAM-mediated alkylation followed by purification and quantitative MS analysis, we confirmed that METTL21A labels HSP70 family proteins. Furthermore, we demonstrated that METTL10 also methylates the eukaryotic elongation factor EF1A1 in mammalian cells. Subsequent biochemical characterization revealed that METTL10 specifically trimethylates EF1A1 at lysine 318 and that siRNA-mediated knockdown of METTL10 decreases EF1A1 methylation levels in vivo. Thus, our study emphasizes the utility of the synthetic cofactor ProSeAM as a chemical probe for the identification of non-histone substrates of KMTs.
Assuntos
Histona-Lisina N-Metiltransferase/química , Histona-Lisina N-Metiltransferase/metabolismo , S-Adenosilmetionina/análogos & derivados , S-Adenosilmetionina/química , Selênio/química , Animais , Células HEK293 , Humanos , Microscopia de Fluorescência , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
When 2,4-dimethylphenol is anodically treated, a dehydrotetramer with four contiguous stereocentres is readily obtained on a multi-gram scale. The substitution of a 2,4-dimethyl-phenoxy fragment by several amines was demonstrated, and the best results were obtained with primary amines. Optically pure α-chiral aliphatic amines yield diastereomeric mixtures that can be separated in most cases. The basic amine causes a partial hemiketal-opening of the bisbenzofuran moiety leading to an equilibrium within an α,ß-unsaturated cyclohexenone. This dynamic behaviour occurs on the time scale of NMR spectroscopy and is also found by X-ray analysis providing a consistent picture.
