The Scientific Oktoberfest will be this years meeting point for some of the internationally most distinguished researchers in the field of Chemistry & Chemical Biology. The CIPSM Scientific Oktoberfest will be held from the 19th to the 20th of September in the Department of Chemistry of the Ludwig-Maximilians-Universität (LMU) München. At the two-day ...

Protein synthesis in all cells is carried out by macromolecular machines called ribosomes. Although the structures of prokaryotic, yeast and protist ribosomes have been determined, the more complex molecular architecture of metazoan 80S ribosomes has so far remained elusive. Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes ...

Trifunctional biotin reagents incorporating cleavable linkers are evaluated for their usage in protein enrichment. A linker based on the Dde protecting group leads to efficient release of protein targets under mild conditions. It additionally contains a masked trypsin cleavage site, which eliminates the majority of the tag during tryptic digestion.

Cohesin plays an important role in chromatid cohesion and has additional functions in higher-order chromatin organization and in transcriptional regulation. The binding of cohesin to euchromatic regions is largely mediated by CTCF or the mediator complex. However, it is currently unknown how cohesin is recruited to pericentric heterochromatin in mammalian ...

Significant advances during the last decade in the field of small-molecule modulators of protein–protein interactions have raised general awareness of the fact that the modulation of protein–protein interactions has tremendous potential for both basic and applied science.[1] Some of the most advanced orthosteric inhibitors of protein–protein ...

Many processes in the regulation of gene expression and signaling involve the formation of protein complexes involving multi-domain proteins. Individual domains that mediate protein-protein and protein-nucleic acid interactions are typically connected by flexible linkers, which contribute to conformational dynamics and enable the formation of complexes with ...

Histone lysine (K) methylation has been shown to play a fundamental role in modulating chromatin architecture and regulation of gene expression. Here we report on the identification of histone H3K56, located at the pivotal, nucleosome DNA entry/exit point, as a novel methylation site that is evolutionary conserved. We identify trimethylation of H3K56 ...

Resistance to drugs targeting human thymidylate synthase (TS) poses a major challenge in the field of anti-cancer therapeutics. Overexpression of the TS protein has been implicated as one of the factors leading to the development of resistance. Therefore, repressing translation by targeting the TS mRNA could help to overcome this problem. In this study, we ...

We report an efficient synthesis of the hypermodified natural tRNA modifications wybutosine (yW) and hydroxywybutosine (OHyW). We also describe the preparation of isotopically labeled analogues for precise quantification of yW and OHyW in different tissues including plant materials. The synthesis involved the formation of the unusual tricyclic ring structure ...

Antimicrobial peptides are important defense compounds of higher organisms that can be used as therapeutic agents against bacterial and/or viral infections. We designed several antimicrobial peptides containing hydrophobic and positively charged clusters that are active against plant and human pathogens. Especially peptide SP1-1 is highly active with a MIC ...

Covalent chemical probes enable investigation of a desired fraction of the proteome. It is possible to adjust the selectivity of these probes, so they either react with a certain amino acid in all proteins, a class of proteins or only a single protein species. A combination of specific reactive groups with additional recognition elements can fine tune probes ...

This study examines the absolute quantification of particle uptake into cells. Methods: We developed a novel method to analyze stacks of confocal fluorescence images of single cells interacting with nano- and micro-particles. Particle_in_Cell-3D is a freely available ImageJ macro. During the image analysis routine, single cells are reconstructed in 3D and ...

Rhomboid proteases are evolutionary conserved intramembrane serine proteases. Because of their emerging role in many important biological pathways, rhomboids are potential drug targets. Unfortunately, few chemical tools are available for their study. Here, we describe a mass spectrometry-based assay to measure rhomboid substrate cleavage and inhibition. We ...

DEAF-1 is an important transcriptional regulator that is required for embryonic development and is linked to clinical depression and suicidal behavior in humans. It comprises various structural domains, including a SAND domain that mediates DNA binding and a MYND domain, a cysteine-rich module organized in a Cys4-Cys2-His-Cys (C4-C2HC) tandem zinc binding ...

Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. Nuclear DNA is packaged into chromatin, and thus genome maintenance can be influenced by distinct chromatin environments. In particular, post-translational modifications of histones have emerged as key regulators of genomic integrity. ...

The circadian clock is constituted by a complex molecular network that integrates a number of regulatory cues needed to maintain organismal homeostasis. To this effect, posttranslational modifications of clock proteins modulate circadian rhythms and are thought to convert physiological signals into changes in protein regulatory function. To explore ...

The tumor suppressor protein p53 is often referred to as the guardian of the genome. In the past, controversial findings have been presented for the role of the C-terminal regulatory domain (RD) of p53 as both a negative regulator and a positive regulator of p53 activity. However, the underlying mechanism remained enigmatic. To understand the function of the ...

Co-transcriptional pre-mRNA processing relies on reversible phosphorylation of the carboxyl-terminal domain (CTD) of Rpb1, the largest subunit of RNA polymerase II (RNAP II). In this study, we replaced in live cells the endogenous Rpb1 by S2A Rpb1, where the second serines (Ser2) in the CTD heptapeptide repeats were switched to alanines, to prevent ...

Oligonucleotides used in gene therapy and silencing are fragile compounds that degrade easily in biological environments. Porous biocompatible carrier particles may provide a useful strategy to deliver these therapeutics to their target sites. Development of appropriate delivery vehicles, however, requires a better understanding of the oligonucleotide-host ...

DNA methylation patterns change dynamically during mammalian development and lineage specification, yet scarce information is available about how DNA methylation affects gene expression profiles upon differentiation. Here we determine genome-wide transcription profiles during undirected differentiation of severely hypomethylated (Dnmt1−/−) embryonic stem ...