Louis Kahn, der Architekt des Salk Institute in La Jolla, sagte einmal:1 „Ein ganz gewöhnlicher, ordinärer Backstein möchte mehr sein als er ist“. Man stelle sich vor, das träfe auch auf Moleküle zu. Wir wissen, dass sie aggregieren können und es tun; bilden komplexe Strukturen erhalten dabei neue Eigenschaften – Funktionen, die man bei Untersuchung einzelnen Komponenten nicht sieht. Dieser Aufsatz beschäftigt mit Molekülaggregaten einer bestimmten Art, solchen, andere oder weniger...

A combination of a chemical double-mutant cycle and linear free energy relationship has demonstrated that weak attractive interaction (−0.8 to −1.5 kJ mol−1) exists between an organic fluorine substituent the face amide functional group (see picture). This study supports recent results have suggested such attraction may be operative in enzyme–inhibitor interactions. Supporting information for this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z460781_s.pdf...

1H NMR spectroscopic data and complementary theoretical predictions suggest that a designed receptor exhibits the anion–π interaction in solution.

First discovered over 60 years ago, post-translational methylation was considered an irreversible modification until the initial discoveries of demethylase enzymes in 2004. Now researchers understand that this process serves as a dynamic and complex control mechanism is misregulated numerous diseases. Lysine most often found on histone proteins can effect gene regulation, epigenetic inheritance, cancer. Because connection to disease, many responsible for are targets new cancer therapies....

The histone code refers to the complex network of post-translational modifications that control gene expression and are high interest as drivers a large number human diseases. We report here on mix-and-match toolkit readily available dyes calixarene host molecules can be combined form dye-displacement sensors respond wide variety cationic peptides. Using data from only two or three such simple supramolecular chemical sensor array produces fingerprints discriminate robustly among many kinds...

We report here a peptide-driven approach to create first inhibitors of the chromobox homolog 7 (CBX7), methyllysine reader protein. CBX7 uses its chromodomain bind histone 3, lysine 27 trimethylated (H3K27me3), and this recognition event is implicated in silencing multiple tumor suppressors. Small trimethyllysine containing peptides were used as basic scaffold from which potent ligands for disruption CBX7-H3K27me3 complex developed. Potency was determined by fluorescence polarization and/or...

Programming and controlling molecular recognition in aqueous solutions is increasingly common, but creating supramolecular sensors that detect analytes biologically relevant remains a nontrivial task. We report here parallel synthesis-driven approach to create family of self-assembling dimeric we call DimerDyes its use for the rapid identification salt-tolerant illicit drugs. developed an efficient method involves synthesis screening crude form without need purify each potential sensor....

Pinning the tail: The post-translational methylation of proteins governs important biochemical pathways, including many involved in gene regulation and cancer. We report here on ability well known p-sulfonatocalix[4]arene to bind strongly trimethyllysine with good selectivity over all other cationic side chains (see figure), post-translationally methylated Arg. also find that it binds site selectively low μM affinity Lys(Me3) residue a representative histone tail peptide. Detailed facts...

Significance Pectin and alginate are polysaccharides found in the cell walls of plants brown algae, respectively. These largely consist chains uronates, which can be metabolized by bacteria through a pathway enzymatic steps to key metabolite 2-keto-3-deoxygluconate (KDG). Understanding metabolism these sugars is important because pectin degradation used many plant-pathogenic during infection, both represent abundant sources carbohydrate for production biofuels. Here we demonstrate that KdgF,...

Many indicator displacement assays can detect biological analytes in water, but these often have reduced performance the presence of an unavoidable component: NaCl. We report here a new self-assembled sensor, DimerDye, that uses novel photochemical guest-sensing mechanism and is intrinsically tolerant cosolutes. synthetically integrated dye into calixarene macrocycle, forming two merocyanine calixarenes (MCx-1 MCx-2). Both compounds self-assemble nonemissive dimers water. The addition good...

X-ray crystallography reveals how a calixarene can bind to dimethyllysine form complex with features similar the aromatic cage motif of chromodomain bound histone tail.

Polycomb repressive complex 1 (PRC1) is critical for mediating gene expression during development. Five chromobox (CBX) homolog proteins, CBX2, CBX4, CBX6, CBX7, and CBX8, are incorporated into PRC1 complexes, where they mediate targeting to trimethylated lysine 27 of histone H3 (H3K27me3) via the N-terminal chromodomain (ChD). Individual CBX paralogs have been implicated as drug targets in cancer; however, high similarities sequence structure among ChDs provide a major obstacle developing...

We describe here the synthesis and characterization of a molecular receptor that forms kinetically thermodynamically stable host−guest complexes in water. This cavitand-based host is composed preorganized aromatic pocket whose rim decorated with four negatively charged carboxylate groups. 1H NMR isothermal titration calorimetry have been used to characterize behavior resulting response changes pH, buffer identity, salt concentration presence sodium dodecyl sulfate micelles.

Synthetic molecular receptors that completely surround their target molecules can be created through the use of noncovalent interactions. These capsules selectively sequester guest from influence bulk solvent and other on basis size, shape, chemical complementarity. This reversible isolation spawns unique behavior within confines host; catalysis reactions stabilization reactive species are possible outcomes have been recently demonstrated. Compartmentalization reagents also a dramatic effect...

Clamping down: A new class of aspartic protease inhibitors that target the malarial family Plasmepsin are reported. These ligands utilize a novel "diamine clamp" to engage catalytic dyad. They potent plasmepsins I, II, and IV, while retaining good selectivity against closely related human cathepsins D E. Supporting information for this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z504119_s.pdf or from author. Please note: The publisher not responsible...

Post-translational modifications of proteins (including phosphorylation, acetylation and methylation, among others) frequently carry out their biological functions by serving as 'on' switches for protein–protein interactions. As highly localized perfectly defined hot-spots binding, they are a diverse set motifs that collectively offer great promise targets therapeutic intervention fundamental studies chemical biology. Recent years have seen the discovery very large number such modification...

A synthetic route to produce a new family of trisulfonated calix[4]arenes bearing single group, selectively introduced, that lines the binding pocket is reported. Ten examples, including sulfonamide and biphenyl-substituted hosts, each with additional elements, demonstrate tuning guest affinities selectivities. NMR titrations in phosphate-buffered water show one hosts binds modified amino acid trimethyllysine highest affinity selectivity observed date.

The polycomb paralogs CBX2, CBX4, CBX6, CBX7, and CBX8 are epigenetic readers that rely on "aromatic cage" motifs to engage their partners' methyllysine side chains. Each CBX carries out distinct functions, yet each includes a highly similar methyllysine-reading chromodomain as key element. CBX7 is the only has been targeted by chemical inhibition. We report small set of peptidomimetic agents in which simple modification switches ligands from one with promiscuity across all provides...

The identification of protein ligands from a DNA-encoded library is commonly conducted by an affinity selection assay. These assays are often not validated for robustness, raising questions about selections that fail to identify and the utility enrichment values ranking ligand potencies. Here, we report method optimizing utilizing potent selective peptidic highly related chromodomains CBX proteins. To optimize parameters, statistical analyses (Z′ factors) were used define ability assay...

Abstract Antibiotic resistance is recognized as an imminent and growing global health threat. New antimicrobial drugs are urgently needed due to the decreasing effectiveness of conventional small‐molecule antibiotics. Antimicrobial peptides (AMPs), a class host defense peptides, emerging promising candidates address this need. The potential sequence space amino acids combinatorially vast, making it possible extend current arsenal agents with practically infinite number new peptide‐based...

Four negative charges at the entrance of a deep pocket, lined with aromatic residues are features synthetic receptor which shows high affinity for acetylcholine (see picture) and choline in water. The size, shape, charge recognition elements featured natural enzyme acetylcholinesterase reproduced by receptor.

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationDiversity and Selection in Self-Assembled Tetrameric CapsulesFraser Hof, Colin Nuckolls, Julius RebekView Author Information The Skaggs Institute for Chemical Biology Department of Chemistry Scripps Research Institute, 10550 North Torrey Pines Road La Jolla, California 92037 Cite this: J. Am. Chem. Soc. 2000, 122, 17, 4251–4252Publication Date (Web):April 14, 2000Publication History Received11 February 2000Published online14 April inissue 1 May...