Journals
2025 EN
Sun MengQi · Zhai ShiJing · Nie Jing
+6 more
Abstract In this study, we disclose an innovative strategy to access α‐monofluoromethyl secondary alcohol derivatives under mild blue‐light irradiation from brominated fluoroethanol benzoate (BFEB). This reaction takes advantages of bulky silicon radical as a halogen atom transfer (XAT) acceptor to generate the nucleophilic monofluoromethyl ketyl‐type radical, which serves as the key intermediate to couple with a series of phenylsulfonyl‐masked substrates. A broad scope of allyl, alkenyl (Z and E configurations), and alkynyl α‐monofluoromethyl carbinol derivatives were obtained in moderate to good yields.
Journals
2025 EN
Köpfler David M. · Hanselmann Paul · Bersier Michaël
+6 more
The synthesis of peptide‐based linkers for antibody‐drug conjugates involves an oxidative decarboxylation step. Traditional Hofer–Moest electrolysis conditions are not suitable to achieve this transformation due to the presence of an oxidatively labile Fmoc‐protecting group. Herein, a solvent‐enabled electrochemical procedure has been established, whereby the solvent electrochemical window prevents degradation of the protecting group. The method has been demonstrated for several relevant peptides in good to very good yields (64–92%).
Journals
2025 EN
Florès Océane · Berthomé Yann · Weiss Lucille
+8 more
Abstract Fluorogenic dimers enable background‐free imaging of biological targets under wash‐free conditions owing to a strong fluorescence enhancement in the apolar cell microenvironment. However, it is crucial that the imaging probe interacts solely with the target receptor to avoid nonspecific interactions and ensure detection with a high signal‐to‐noise ratio. Herein, we describe a convenient and rapid approach for the synthesis of various functionalized cyanine dyes by click chemistry allowing the fine‐tuning of the physicochemical and fluorogenic properties of the dimers. A structure‐interaction relationship study was conducted for the fluorogenic dimers in the presence of bovine serum albumin (BSA) and liposomes as models of serum proteins and cell membranes. We identified d─Cy─E which combined the lowest nonspecific interactions with the optimal fluorescence turn‐on properties. By conjugating d─Cy─E to a peptide ligand of the apelin GPCR, we developed Ap─d─Cy─E , the first fluorescent turn‐on probe for the background‐free imaging of this receptor in living cells.
Journals
2025 EN
Li Yang · Figueirêdo de Alcântara Morais Sara · Han Mingyang
+9 more
Abstract Four cis ‐chelating diphosphanes derived from cyclodextrins (CDs), each featuring a distinct intracavity environment, compel Ni II or Pd II metal centers to reside within α ‐ or β ‐CD cavities. Nickel(II) complexes of these metal‐confining ligands act as active catalysts in ethylene oligomerization upon activation with modified methylaluminoxane (MMAO). The size of the cavity and the position of the P 2 Ni fragment relative to the cavity affect both the activity and selectivity of the reaction. In all instances, 1‐butene is the major product (up to 98% C4 products and 90% 1‐butene within the C 4 fraction). Extensive theoretical studies with state‐of‐the‐art methods carried out on the most selective system suggest that the CD cavity restricts isomerization pathways by limiting the mobility of the coordinated olefin in this constrained supramolecular environment, thereby enhancing α ‐olefin formation.
Journals
2025 EN
Maujean Timothé · Van Wesemael Camille · Tual Laurine
+5 more
Abstract We report an efficient double‐click strategy combining copper‐catalyzed azide–alkyne cycloaddition (CuAAC) with (thia‐)Diels–Alder (DA) reactions, enabled by newly designed heterobifunctional platforms bearing orthogonal clickable groups: alkyne–dithioester, alkyne–maleimide, or azide–diene. These platforms were evaluated through both one‐pot sequential protocols (CuAAC/DA or CuAAC/thia‐DA) and three‐component reactions (3CR), using model substrates with complementary functionalities. The use of a highly reactive s‐cis ‐constrained exocyclic diene, enabled rapid cycloadditions with maleimide or phosphonodithioester dienophiles. All reactions were performed under mild, biocompatible conditions (37 °C, 1:1 H₂O/ i PrOH, 1–2 hours), and most afforded the desired conjugates in good isolated yields. The methodology was further validated through the successful bioconjugation of three small peptides with either a fluorophore or biotin, demonstrating its efficiency, versatility, and compatibility with biologically relevant functional groups.
Journals
2025 DE
Rosenberg Dominique · Wagner Tom · Hallmann Anne
Abstract Eisen ist ein zentraler Rohstoff für die Herstellung zahlreicher Alltagsprodukte wie Besteck, Fahrzeuge und Kochtöpfe. Die Eisen‐ und Stahlindustrie stellt daher einen bedeutenden, jedoch energieintensiven Industriezweig in Deutschland dar, der erhebliche Mengen an Kohlenstoffdioxid (CO 2 ) freisetzt. Ein aktuelles Pilotprojekt untersucht den Einsatz von grünem Wasserstoff als alternatives Reduktionsmittel im Hochofenprozess, um die CO 2 ‐Emissionen bei der Eisenproduktion zu senken. Der folgende Kurzartikel stellt ein vereinfachtes Experiment vor, das den Hochofenprozess mit Wasserstoff im Unterricht veranschaulicht und didaktisch aufbereitet integriert.
Journals
2025 DE
Rosenberg Dominique · Wagner Tom · Hallmann Anne
Der Einsatz von grünem Wasserstoff als Reduktionsmittel im Hochofenprozess könnte in Zukunft eine Alternative für die Eisenproduktion sein. Auf dem Titelbild sowie im Kurzartikel von Rosenberg et al. ab S. 197 wird ein einfacher Modellversuch dargestellt, welcher den Hochofenprozess mit Wasserstoff im Unterricht veranschaulicht und didaktisch aufbereitet integriert.
Journals
2025 EN
Lyothier Isabelle · Diethelm Stefan · Pothier Julien
+13 more
EP2 is a G‐protein coupled receptor that is activated by prostaglandin E2 (PGE2). Signaling through the EP2 receptor has been shown to play a key role in various processes involved in diseases such as immune disorders or cancer. A new class of selective EP2 antagonists with an attractive in vitro and in vivo profile has been identified. The amide bond in the original screening hit is replaced by various alternatives. The introduction of an aminopyrimidine scaffold results in excellent potency. Improvement of physicochemical and ADME properties is achieved by incorporation of a carboxylic acid moiety, resulting in lead compound 29 exhibiting drug‐like properties.
Journals
2025 EN
Lyothier Isabelle · Diethelm Stefan · Pothier Julien
+13 more
Prostaglandin E2 (PGE2) signaling via receptors prostaglandin E2 receptor 2 (EP2) and prostaglandin E2 receptor 4 (EP4) is involved in various aspects of cancer and has been shown to promote tumor progression, metastasis, and immune evasion. Inhibition of PGE2 signaling by blockade of the EP2 and EP4 receptors has the potential to counteract the tumor‐promoting effects of PGE2. Herein, the discovery of compound 30 (ACT‐1002‐4271), a dual EP2/EP4 antagonist with single‐digit nanomolar potency on both receptors, is presented. The medicinal chemistry strategy is based on fine‐tuning of the substitution pattern on an EP2 selective starting point to achieve dual EP2/EP4 antagonism. ACT‐1002‐4271 demonstrated significant antitumor efficacy in an experimental mammary tumour‐6 mouse model when administered subcutaneously.
Journals
2025 EN
Bertucci Alexandre · Dufour Ondine · Appay Romain
+19 more
Abstract Background Brain tumors represent one of the main causes of cancer‐related mortality in young patients. Among them, oligodendrogliomas (OG) are adult‐type diffuse gliomas with the best prognosis. Nevertheless, characterization of these tumors in the young population remains poorly documented. Our objective was to characterize the population of young adults under 40 years of age with grade 3 OG in the POLA cohort. Methods Clinical data prospectively collected for all patients registered with grade 3 OG between April 2009 and August 2021 were extracted from the national POLA database. This study compared the patient subgroup <40 years of age to the one >40 years of age. Results The authors included 111 patients <40 years old and 363 patients ≥40 years old. Treatment received did not differ significantly between the two subgroups. Temporal location was more frequent in older patients ( p = .009). Patients <40 years old presented more often seizure as initial symptom ( p = .003). They had less frequent chromosome 9p loss ( p < .001) and less CDKN2A homozygous deletion ( p = .024). Median progression‐free survival (PFS) was 123 months (range, 86–not reached [NR]) versus 88 months (range, 67–117) ( p = .082) and median overall survival (OS) was not reached (range, 147–NR) versus 163 months (range, 137–NR) ( p < .001) in younger and older subgroups, respectively. In multivariate analysis, complete or subtotal resection ( p = .014) and seizure at diagnosis ( p = .032) were associated with better OS. Conclusion Young patients with grade 3 OG have distinct clinical presentation, molecular features, and outcomes compared to the older patients.