Glucosinolates are plant thioglucosides, which act as chemical defenses. Upon tissue damage, their myrosinase-catalyzed hydrolysis yields aglucones that rearrange to toxic isothiocyanates. Specifier proteins such as thiocyanate-forming protein from Thlaspi arvense (TaTFP) are non-heme iron proteins, which capture the aglucone to form alternative products, e.g. nitriles or thiocyanates. To resolve the electronic state of the bound iron cofactor in TaTFP, we applied continuous wave electron paramagnetic resonance (CW EPR) spectroscopy at X-and Q-band frequencies (∼9.4 and ∼34 GHz). We found characteristic features of high spin and low spin states of a d5 electronic configuration and local rhombic symmetry during catalysis. We monitored the oxidation states of bound iron during conversion of allylglucosinolate by myrosinase and TaTFP in presence and absence of supplemented Fe2+. Without added Fe2+, most high spin features of bound Fe3+ were preserved, while different g’-values of the low spin part indicated slight rearrangements in the coordination sphere and/or structural geometry. We also examined involvement of the redox pair Fe3+/Fe2 in samples with supplemented Fe2+. The absence of any EPR signal related to Fe3+ or Fe2+ using an iron-binding deficient TaTFP variant allowed us to conclude that recorded EPR signals originated from the bound iron cofactor.

In contrast to the myriad of methods available to produce α‐helices and antiparallel β‐sheets in synthetic peptides, just a few are known for the construction of stable, non‐cyclic parallel β‐sheets. Herein, we report an efficient on‐resin approach for the assembly of parallel β‐sheet peptides in which the N‐alkylated turn moiety enhances the stability and gives access to a variety of functionalizations without modifying the parallel strands. The key synthetic step of this strategy is the multicomponent construction of an N‐alkylated turn using the Ugi reaction on varied isocyano‐resins. This four‐component process assembles the orthogonally protected turn fragment and incorporates handles serving for labeling/conjugation purposes or for reducing peptide aggregation. NMR and circular dichroism analyses confirm the better‐structured and more stable parallel β‐sheets in the N‐alkylated peptides compared to the non‐functionalized variants.

For the first time, the Petasis (borono‐Mannich) reaction is employed for the multicomponent labeling and stapling of peptides. The report includes the solid‐phase derivatization of peptides at the N‐terminus, Lys, and Nϵ‐MeLys side‐chains by an on‐resin Petasis reaction with variation of the carbonyl and boronic acid components. Peptides were simultaneously functionalized with aryl/vinyl substituents bearing fluorescent/affinity tags and oxo components such as dihydroxyacetone, glyceraldehyde, glyoxylic acid, and aldoses, thus encompassing a powerful complexity‐generating approach without changing the charge of the peptides. The multicomponent stapling was conducted in solution by linking Nϵ‐MeLys or Orn side‐chains, positioned at i, i+7 and i, i+4, with aryl tethers, while hydroxy carbonyl moieties were introduced as exocyclic fragments. The good efficiency and diversity oriented character of these methods show prospects for peptide drug discovery and chemical biology.

Die Funktionalisierung von C‐H‐Bindungen mit Nichtedelmetallkatalysatoren ist ein wichtiges Forschungsgebiet für die Entwicklung effizienter und nachhaltiger Synthesemethoden. In diesem Artikel beschreiben wir die Entwicklung Eisenporphyrin‐katalysierter Reaktionen von Diazoacetonitril mit N‐Heterocyclen um so einen Zugang zu wertvollen Vorläufern zu Tryptaminen zu erhalten. Darüberhinaus berichten wir über experimentelle mechanistische Studien sowie über konzeptionelle Studien zu einer enzymatischen Synthese mit dem Enzym YfeX. Mit dem leicht zugänglichen FeTPPCl‐Katalysator konnten wir hoch effiziente C‐H‐Funktionalisierungsreaktionen von Indol und Indazol‐Heterocyclen zeigen. Diese Reaktionen können unter milden Reaktionsbedingungen, mit exzellenten Ausbeuten und großer Toleranz funktioneller Gruppen inklusive Anwendungen im Grammmaßstab durchgeführt werden und eröffnen so einen einzigartigen, effizienten Zugang zu Tryptaminen.

An important development in the field of macrocyclization strategies towards molecular cages is described. The approach comprises the utilization of a double Ugi four‐component macrocyclization for the assembly of macromulticycles with up to four different tethers, that is, hybrid cages. The innovation of this method rests on setting up the macromulticycle connectivities not through the tethers but through the bridgeheads, which in this case involve N‐substituted amino acids. Both dilution and metal‐template‐driven macrocyclization conditions were implemented with success, enabling the one‐pot formation of cryptands and cages including steroidal, polyether, heterocyclic, peptidic, and aryl tethers. This method demonstrates substantial complexity‐generating character and is suitable for applications in molecular recognition and catalysis.

In an endeavor to provide an efficient route to natural product hybrids, described herein is an efficient, highly stereoselective, one‐pot process comprising an organocatalytic conjugate addition of 1,3‐dicarbonyls to α,β‐unsaturated aldehydes followed by an intramolecular isocyanide‐based multicomponent reaction. This approach enables the rapid assembly of complex natural product hybrids including up to four different molecular fragments, such as hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties. The strategy combines the stereocontrol of organocatalysis with the diversity‐generating character of multicomponent reactions, thus leading to structurally unique peptidomimetics integrating heterocyclic, lipidic, and sugar moieties.

Conditional gene expression and modulating protein stability under physiological conditions are important tools in biomedical research. They led to a thorough understanding of the roles of many proteins in living organisms. Current protocols allow for manipulating levels of DNA, mRNA, and of functional proteins. Modulating concentrations of proteins of interest, their post-translational processing, and their targeted depletion or accumulation are based on a variety of underlying molecular modes of action. Several available tools allow a direct as well as rapid and reversible variation right on the spot, i.e., on the level of the active form of a gene product. The methods and protocols discussed here include inducible and tissue-specific promoter systems as well as portable degrons derived from instable donor sequences. These are either constitutively active or dormant so that they can be triggered by exogenous or developmental cues. Many of the described techniques here directly influencing the protein stability are established in yeast, cell culture and in vitro systems only, whereas the indirectly working promoter-based tools are also commonly used in higher eukaryotes. Our major goal is to link current concepts of conditionally modulating a protein of interest’s activity and/or abundance and approaches for generating cell and tissue types on demand in living, multicellular organisms with special emphasis on plants.

Das große therapeutische Potenzial eines Organozinn(IV)‐beladenen nanostrukturierten SiO2 (SBA‐15pSn) wird am Beispiel der Rückbildung eines durch B16‐Zellen induzierten Melanoms bei syngenen C57BL/6‐Mäusen demonstriert. Neben Apoptose als grundlegendem Mechanismus der Antitumorwirkung einer Vielzahl von Chemotherapeutika ist der entscheidende Vorteil dieses mesoporösen zinnhaltigen Materials das Auslösen der Zelldifferenzierung – ein Effekt, der weder für metallbasierte Zytostatika noch für mesoporöse Materialien alleine bisher beobachtet wurde. Dieser nichtaggressive Wirkungsmechanismus ist hochwirksam gegen Tumorzellen aber im gewählten Konzentrationsbereich nichttoxisch für normales Gewebe. JNK‐unabhängige Apoptose (JNK: Jun amino‐terminal kinase), begleitet von der Bildung des melanozytenartigen nichtproliferativen Phänotyps der überlebenden Zellen demonstriert das außergewöhnliche Potenzial von SBA‐15pSn zur Unterdrückung von Tumorwachstum ohne eine unerwünschte kompensatorische Proliferation der erkrankten Zellen als Antwort auf den Zelltod in ihrer Nachbarschaft.

Ein uraltes Reaktionsgefäß: TobZ carbamoyliert das Antibiotikum Tobramycin unter Bildung von Nebramycin‐5′. Dabei katalysiert die YrdC‐ähnliche Domäne (blau) die Bildung eines intermediären Carbamoyladenylats, das innerhalb einer tunnelartigen Reaktionskammer zur Kae1‐ähnlichen Domäne (braun), dem Ort des Carbamoyltransfers, transferiert wird.

Durch Reaktion primärer Amine mit funktionalisierten α,α‐Dichlortosylhydrazonen unter milden Bedingungen gelingt eine „spurlose“ Tosylhydrazon‐basierte Triazolsynthese, die ausschließlich zur Bildung 1,4‐substituierter Triazol‐„Klick‐Produkte“ unter vollständigem Konfigurationserhalt am Stereozentrum führt. Primäre Amine, die in vielen Naturstoffen vorkommen, können chemoselektiv ohne die Notwendigkeit einer umfassenden Schutzgruppenstrategie modifiziert werden.