Publications

Receptor avidity through multivalency is a highly sought-after property of ligands. While readily available in nature in the form of bivalent antibodies, this property remains challenging to engineer in synthetic molecules. The discovery of several bivalent venom peptides containing two homologous and independently folded domains (in a tandem repeat arrangement) has provided a unique opportunity to better understand the underpinning design of ...

In the past decades an increasing number of studies revealed that G protein-coupled receptors (GPCRs) are capable of forming dimers or even higher-ordered oligomers, which may modulate receptor function and act as potential drug targets. In this review, we briefly summarized the design strategy of bivalent GPCR ligands and mainly focused on how to use them to study and/or detect GPCP dimerization in vitro and in vivo. Bivalent ligands show ...

Several gold +I and +III complexes are investigated computationally and spectroscopically, focusing on the d-configuration and physical oxidation state of the metal center. Density functional theory calculations reveal the non-negligible electron-sharing covalent character of the metal-to-ligand sigma-bonding framework. The bonding of gold(III) is shown to be isoelectronic to the formal Cu-III complex [Cu(CF3)(4)](1-), in which the metal center ...

Various purine-based nucleoside analogues have demonstrated unexpected affinity for nonpurinergic G protein-coupled receptors (GPCRs), such as opioid and serotonin receptors. In this work, we synthesized a small library of new 7-deazaadenosine and pyrazolo-[3,4-d]-pyrimidine riboside analogues, featuring dual C7 and N-6 modifications and assessed their affinity for various GPCRs. During the course of the synthesis of 7-ethynyl ...

Aurora kinase A (AURKA) is a well-established target in neuroblastoma (NB) due to both its catalytic functions during mitosis and its kinase-independent functions, including stabilization of the key oncoprotein MYCN. We present a structure-activity relationship (SAR) study of MK-5108-derived PROTACs against AURKA by exploring different linker lengths and exit vectors on the thalidomide moiety. PROTAC SK2188 induces the most potent AURKA ...

Despite its practical importance, organoiron chemistry remains poorly understood due to its mechanistic complexity. Here, we focus on the oxidative addition of organyl halides to phenylferrate anions in the gas phase. By mass-selecting individual phenylferrate anions, we can determine the effect of the oxidation state, the ligation, and the nuclearity of the iron complex on its reactions with a series of organyl halides RX. We find that Ph2 ...

Recent advances in alkaline earth (Ae) metal hydrogenation catalysis have broadened the spectrum of potential catalysts to include candidates from the main group, providing a sustainable alternative to the commonly used transition metals. Although Ae-amides have already been demonstrated to catalyze hydrogenation of imines and alkenes, a lucid understanding of how different metal/ligand combinations influence the catalytic activity is yet to be ...

The CXC chemokine receptor 4 (CXCR4) is a well-described G protein-coupled receptor (GCPR) that is involved in different physio-pathological processes upon binding of its endogenous ligand CXC chemokine 12 (CXCL12). CXCR4 is expressed throughout development and adulthood on a variety of cell types including lymphocytes, endothelial, epithelial and hematopoietic stem cells (HSCs). CXCR4 plays a fundamental physiological role in hematopoiesis, ...

BACKGROUND: Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multicentre cohort studies. METHODS: The Outcomes After Kidney injury in Surgery (OAKS) prognostic ...

N-heterocyclic carbenes (NHCs) have been extensively used as ligands in organometallic complexes of the Transition Metals. This review focuses on manganese complexes bearing these NHC ligands. An overview is given of all complexes of manganese in various oxidation states, as well as their use in catalytic reactions, principally in CO2 reduction, hydrosilylation and alkylation. (C) 2021 Published by Elsevier Ltd.