Journal: Nature Chemistry

Abbreviation

Nat Chem

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Nature

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1755-4349
1755-4330

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2010 - 2019462020 - 202535
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Publications1 - 10 of 81
  • A multistep single-crystal-to-single-crystal bromodiacetylene dimerization
    Item type: Journal Article
    Hoheisel, Tobias N.; Schrettl, Stephen; Marty, Roman; et al. (2013)
    Nature Chemistry
  • Palladium-catalysed carboformylation of alkynes using acid chlorides as a dual carbon monoxide and carbon source
    Item type: Journal Article
    Lee, Yong Ho; Denton, Elliott; Morandi, Bill (2021)
    Nature Chemistry
    Hydroformylation, a reaction that installs both a C–H bond and an aldehyde group across an unsaturated substrate, is one of the most important catalytic reactions in both industry and academia. Given the synthetic importance of creating new C–C bonds, the development of carboformylation reactions, wherein a new C–C bond is formed instead of a C–H bond, would bear enormous synthetic potential to rapidly increase molecular complexity in the synthesis of valuable aldehydes. However, the demanding complexity inherent in a four-component reaction, utilizing an exogenous CO source, has made the development of a direct carboformylation reaction a formidable challenge. Here, we describe a palladium-catalysed strategy that uses readily available aroyl chlorides as a carbon electrophile and CO source, in tandem with a sterically congested hydrosilane, to perform a stereoselective carboformylation of alkynes. An extension of this protocol to four chemodivergent carbonylations further highlights the creative opportunity offered by this strategy in carbonylation chemistry.
  • A monodomain class II terpene cyclase assembles complex isoprenoid scaffolds
    Item type: Journal Article
    Moosmann, Philipp; Ecker, Felix; Leopold-Messer, Stefan; et al. (2020)
    Nature Chemistry
    Class II terpene cyclases, such as oxidosqualene and squalene-hopene cyclases, catalyse some of the most complex polycyclization reactions. They minimally exhibit a β,γ-didomain architecture that has been evolutionarily repurposed in a wide range of terpene-processing enzymes and likely resulted from a fusion of unidentified monodomain proteins. Although single domain class I terpene cyclases have already been identified, the corresponding class II counterparts have not been previously reported. Here we present high-resolution X-ray structures of a monodomain class II cyclase, merosterolic acid synthase (MstE). With a minimalistic β-domain architecture, this cyanobacterial enzyme is able to construct four rings in cytotoxic meroterpenoids with a sterol-like topology. The structures with bound substrate, product, and inhibitor provide detailed snapshots of a cyclization mechanism largely governed by residues located in a noncanonical enzyme region. Our results complement the few known class II cyclase crystal structures, while also indicating that archaic monodomain cyclases might have already catalyzed complex reaction cascades.
  • Deciphering functional roles of protein succinylation and glutarylation using genetic code expansion
    Item type: Journal Article
    Weyh, Maria; Jokisch, Marie-Lena; Nguyen, Tuan-Anh; et al. (2024)
    Nature Chemistry
    Post-translational modifications (PTMs) dynamically regulate cellular processes. Lysine undergoes a range of acylations, including malonylation, succinylation (SucK) and glutarylation (GluK). These PTMs increase the size of the lysine side chain and reverse its charge from +1 to -1 under physiological conditions, probably impacting protein structure and function. To understand the functional roles of these PTMs, homogeneously modified proteins are required for biochemical studies. While the site-specific encoding of PTMs and their mimics via genetic code expansion has facilitated the characterization of the functional roles of many PTMs, negatively charged lysine acylations have defied this approach. Here we describe site-specific incorporation of SucK and GluK into proteins via temporarily masking their negative charge through thioester derivatives. We prepare succinylated and glutarylated bacterial and mammalian target proteins, including non-refoldable multidomain proteins. This allows us to study how succinylation and glutarylation impact enzymatic activity of metabolic enzymes and regulate protein-DNA and protein-protein interactions in biological processes from replication to ubiquitin signalling.
  • Carbon-to-nitrogen atom swap enables direct access to benzimidazoles from drug-like indoles
    Item type: Journal Article
    Paschke, Ann-Sophie K.; Bragger, Yannick; Botlik, Bence B.; et al. (2025)
    Nature Chemistry
    The ability to selectively edit organic molecules at the atomic level has the potential to streamline lead discovery and optimization in the pharmaceutical and agrochemical industry. While numerous atom insertion and deletion reactions have recently been reported, examples of single atom swaps remain scarce due to the challenge of orchestrating the selective cleavage and formation of multiple chemical bonds around the same atom. Here we report a method for the carbon-to-nitrogen atom swap in N-alkyl indoles, allowing the direct conversion of indoles to the corresponding benzimidazoles. The reaction leverages the innate reactivity of the indole scaffold to engage in an initial oxidative cleavage step, followed by oxidative amidation, Hofmann-type rearrangement and cyclization. This complex sequence of steps is mediated by the simple combination of commercially available phenyliodine(III) diacetate and ammonium carbamate as the nitrogen atom source. The reaction tolerates a wide range of functional groups, which is demonstrated by the interconversion of 15 drug-like molecules, implying its immediate applicability across a wide range of discovery programmes.
  • Charting a course for chemistry
    Item type: Other Journal Item
    Aspuru Guzik, Alán; Baik, Mu-Hyun; Balasubramanian, Shankar; et al. (2019)
    Nature Chemistry
  • Understanding and controlling the substrate effect on graphene electron-transfer chemistry via reactivity imprint lithography
    Item type: Journal Article
    Wang, Qing Hua; Jin, Zhong; Kim, Ki Kang; et al. (2012)
    Nature Chemistry
  • An Oxazetidine Amino Acid for Chemical Protein Synthesis by Rapid, Serine-Forming Ligations
    Item type: Journal Article
    Pusterla, Ivano; Bode, Jeffrey W. (2015)
    Nature Chemistry
    Amide-forming ligation reactions allow the chemical synthesis of proteins by the union of unprotected peptide segments, and enable the preparation of protein derivatives not accessible by expression or bioengineering approaches. The native chemical ligation (NCL) of thioesters and N-terminal cysteines is unquestionably the most successful approach, but is not ideal for all synthetic targets. Here we describe the synthesis of an Fmoc-protected oxazetidine amino acid for use in the α-ketoacid–hydroxylamine (KAHA) amide ligation. When incorporated at the N-terminus of a peptide segment, this four-membered cyclic hydroxylamine can be used for rapid serine-forming ligations with peptide α-ketoacids. This ligation operates at low concentration (100 μM–5 mM) and mild temperatures (20–25 °C). The utility of the reaction was demonstrated by the synthesis of S100A4, a 12 kDa calcium-binding protein not easily accessible by NCL or other amide-forming reactions due to its primary sequence and properties.
  • Gram-scale synthesis of two-dimensional polymer crystals and their structure analysis by X-ray diffraction
    Item type: Journal Article
    Kory, Max J.; Wörle, Michael; Weber, Thomas; et al. (2014)
    Nature Chemistry
Publications1 - 10 of 81