The treatment of cancer through the development of new therapies is one of the most important challenges of our time. The decoding of the human genome has yielded important insights into the molecular basis of physical disorders, and in most cases a connection between failures in specific genes and the resulting clinical symptoms can be made. The modulation of epigenetic mechanisms enables, by definition, the alteration of cellular phenotype without altering the genotype. The information content of a single gene can be crucial or harmful, but the prerequisite for a cellular effect is active gene transcription. To this end, epigenetic mechanisms play a very important role, and the transcription of a given gene is directly influenced by the modification pattern of the surrounding histone proteins as well as the methylation pattern of the DNA. These processes are effected by different enzymes which can be directly influenced through the development of specific modulators. Of course, all genetic information is written as a four-character code in DNA. However, epigenetics describes the art of reading between the lines.
HATs off! The development of the first cell‐permeable small‐molecule inhibitor of the human histone acetyltransferase (HAT) Gcn5 opens up new possibilities for understanding the histone code. Based on kinetic data and the proposed mechanism of the acetylation by Gcn5, the relatively simple butyrolactone structure of the inhibitor was identified.
The determination of the relative configuration of stereogenic centers in organic molecules by NMR spectroscopy is in general an interlinked problem of simultaneous determination of conformation and configuration. This is usually accomplished using distance restraints from NOE data [1]
Syn‐ oder Anti‐pathie: Die relative Konfiguration eines α‐Methylen‐γ‐butyrolactons 1 kann mithilfe dipolarer Restkopplungen (RDCs) bestimmt werden. Konventionelle NMR‐Methoden schlugen fehl, da im Konformationsraum beider Diastereomere Strukturen existieren, die mit den experimentellen NOE‐Daten und 3J‐Kopplungskonstanten in Einklang sind. Aus Messungen von homo‐ and heteronuclearen RDCs und Vergleich mit den möglichen Konformeren kann geschlossen werden, dass 1 trans‐konfiguriert ist.
Lipid-modified proteins play decisive roles in important biological processes such as signal transduction, organisation of the cytoskeleton and vesicular transport. Lipidation of these proteins is essential for correct biological function. Among the modifications with lipids, prenylation and myristoylation are well understood. However, the machinery of palmitoylation is still under investigation. Recently, an enzyme, acyl protein thioesterase 1 (APT1), that may play a regulatory role in the palmitoylation cycle of H-Ras and G-protein alpha subunits, was purified. Motivated by this work, several inhibitors of APT1 were designed, synthesized and biologically evaluated leading to highly active compounds.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.