RESUMO
The activity of transcription factors (TFs) has empowered the reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) and alternative lineages. Elucidation of the molecular mechanisms underpinning these processes has expanded our understanding of how novel gene expression programs become activated while old ones are silenced. How TFs modify chromatin and activate requisite enzymes during these processes has recently been discussed in several excellent reviews. Here we discuss the questions of how ectopically expressed TFs access chromatin to modulate enhancers and establish a novel transcriptome during cell reprogramming, lineage conversions and differentiation.
Assuntos
Diferenciação Celular/genética , Reprogramação Celular/genética , Elementos Facilitadores Genéticos , Células-Tronco Pluripotentes Induzidas/citologia , Linhagem da Célula , Cromatina/genética , Células-Tronco Embrionárias/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Fatores de Transcrição/genética , Transcriptoma/genéticaRESUMO
(2R,3S,1'R)-3-(1-Hydroxy-2-phosphonoethyl)-2-piperidinecarboxyl ic acid 1 has been synthesized by two different methods. The NMDA receptor binding affinities (Ki values) are 74 nM for compound 1, and 64 nM for the corresponding ketone 2. The analgesic effects were evaluated using the mouse hot-plate test and the mouse formalin model. The ED50 values for the racemates of compounds 1 and 2, using the mouse hotplate and intrathecal injection, were 0.53 and 0.51 nmol, respectively.
Assuntos
Analgésicos/síntese química , Analgésicos/farmacologia , N-Metilaspartato/antagonistas & inibidores , Organofosfonatos/síntese química , Organofosfonatos/farmacologia , Ácidos Pipecólicos/síntese química , Ácidos Pipecólicos/farmacologia , Analgésicos/metabolismo , Animais , Sítios de Ligação , Ligação Competitiva , Antagonistas de Aminoácidos Excitatórios/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Cinética , Camundongos , Organofosfonatos/metabolismo , Medição da Dor/efeitos dos fármacos , Ácidos Pipecólicos/metabolismo , Ratos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , EstereoisomerismoRESUMO
A bifunctional hapten was synthesized consisting of a blood group A active tetrasaccharide (A-tetra) and a blood group Le(a) active pentasaccharide lacto-N-fucopentaose II (LNF II), linked to each other with a phenylaminothiourea spacer connecting the reducing ends (A-tetra-LNF II). The hapten was demonstrated to retain both blood group A and Le(a) activity and could be easily bound to both monoclonal anti-A and anti-Le(a) affinity columns. Due to the strong temperature dependence of the two antibodies their binding to oligosaccharides, the bifunctional hapten could be utilized to achieve easy desorption in the final step of affinity purification of either monoclonal anti-Le(a) or anti-A. The system is postulated to have general applicability in affinity purification of any ligate that binds with an avidity too high to achieve non-denaturing desorption.
