Jörg Scheuermann


Last Name

Scheuermann

First Name

Jörg

ORCID

0000-0001-7746-4717

Organisational unit

08641 - Scheuermann, Jörg (Tit.-Prof.) / Scheuermann, Jörg (Tit.-Prof.)

Search Results

Publications 1 - 10 of 90
  • Advancing small-molecule drug discovery by encoded dual-display technologies
    Item type: Review Article
    Lessing, Alice; Petrov, Dimitar; Scheuermann, Jörg (2023)
    Trends in Pharmacological Sciences
    DNA-encoded chemical library technology (DECL or DEL) has become an important pillar for small-molecule drug discovery. The technology rapidly identifies small-molecule hits for relevant target proteins at low cost and with a high success rate, including ligands for targeted protein degradation (TPD). More recently, the setup of DNA- or peptide nucleic acid (PNA)-encoded chemical libraries based on the simultaneous display of ligand pairs, termed dual-display, allows for more sophisticated applications which will be reviewed herein. Both stable and dynamic dual-display DEL technologies enable innovative affinity-based selection modalities, even on and in cells. Novel methods for a seamless conversion between single- and double-stranded library formats allow for even more versatility. We present the first candidates emerging from dual-display technologies and discuss the future potential of dual-display for drug discovery.
  • Isolation of a Small-Molecule Inhibitor of the Antiapoptotic Protein Bcl-xL from a DNA-Encoded Chemical Library
    Item type: Journal Article
    Melkko, Samu; Mannocci, Luca; Dumelin, Christoph E.; et al. (2010)
    ChemMedChem
  • Isolation of a Natural Killer Group 2D Small-Molecule Ligand from DNA-Encoded Chemical Libraries
    Item type: Journal Article
    Dakhel, Sheila; Galbiati, Andrea; Migliorini, Francesca; et al. (2022)
    ChemMedChem
    Natural Killer Group 2D (NKG2D) is a homo-dimeric transmembrane protein which is typically expressed on the surface of natural killer (NK) cells, natural killer T (NKT) cells, gamma delta T (gamma delta T) cells, activated CD8 positive T-cells and activated macrophages. Bispecific molecules, capable of bridging NKG2D with a target protein expressed on the surface of tumor cells, may be used to redirect the cytotoxic activity of NK-cells towards antigen-positive malignant T-cells. In this work, we report the discovery of a novel NKG2D small molecule binder [K-D=(410 +/- 60) nM], isolated from a DNA-Encoded Chemical Library (DEL). The discovery of small organic NKG2D ligands may facilitate the generation of fully synthetic bispecific adaptors, which may serve as an alternative to bispecific antibody products and which may benefit from better tumor targeting properties.
  • Hit-Validation Methodologies for Ligands Isolated from DNA-Encoded Chemical Libraries
    Item type: Journal Article
    Zimmermann, Gunther; Li, Yizhou; Rieder, Ulrike; et al. (2017)
    ChemBioChem
  • Modular assembly and encoding strategies for dual-display DNA-encoded chemical libraries
    Item type: Journal Article
    Oehler, Sebastian; Plais, Louise; Bassi, Gabriele; et al. (2021)
    Chemical Communications
    DNA-encoded chemical libraries (DELs) are increasingly being used for the discovery of protein ligands and can be constructed displaying either one or two molecules at the extremities of the two complementary DNA strands. Here, we describe that DELs, featuring the simultaneous display of two molecules, can be encoded using various types of DNA structures, which go beyond the use of conventional double-stranded DNA fragments. Specifically, we compared dual-display methodologies in hairpin, circular or linear formats in terms of polymerase chain reaction (PCR) amplifiability and performance in affinity capture selections. The methods reported in this article highlight the feasibility and modularity of the described encoding strategies and may thus further expand the scope of DNA-encoded chemistry, particularly for the identification of compounds which recognize adjacent epitopes on the surface of target proteins of interest.
  • Critical Evaluation of Photo-cross-linking Parameters for the Implementation of Efficient DNA-Encoded Chemical Library Selections
    Item type: Journal Article
    Sannino, Alessandro; Gironda-Martínez, Adrián; Gorre, Émile M.D.; et al. (2020)
    ACS Combinatorial Science
  • Discovery of small-molecule interleukin-2 inhibitors from a DNA-encoded chemical library
    Item type: Journal Article
    Leimbacher, Markus; Zhang, Yixin; Mannocci, Luca; et al. (2012)
    Chemistry - A European Journal
  • High-throughput sequencing for the identification of binding molecules from DNA-encoded chemical libraries
    Item type: Journal Article
    Buller, Fabian; Steiner, Martina; Scheuermann, Jörg; et al. (2010)
    Bioorganic & Medicinal Chemistry Letters
  • Selective Fragments for the CREBBP Bromodomain Identified from an Encoded Self‐assembly Chemical Library
    Item type: Journal Article
    Catalano, Marco; Moroglu, Mustafa; Balbi, Petra; et al. (2020)
    ChemMedChem
    DNA‐encoded chemical libraries (DECLs) are collections of chemical moieties individually coupled to distinctive DNA barcodes. Compounds can be displayed either at the end of a single DNA strand (i. e., single‐pharmacophore libraries) or at the extremities of two complementary DNA strands (i. e., dual‐pharmacophore libraries). In this work, we describe the use of a dual‐pharmacophore encoded self‐assembly chemical (ESAC) library for the affinity maturation of a known 4,5‐dihydrobenzodiazepinone ring (THBD) acetyl‐lysine (KAc) mimic for the cyclic‐AMP response element binding protein (CREB) binding protein (CREBBP or CBP) bromodomain. The new pair of fragments discovered from library selection showed a sub‐micromolar affinity for the CREBBP bromodomain in fluorescence polarization and ELISA assays, and selectivity against BRD4(1). © 2020 Wiley-VCH GmbH.
  • Encoded Self-Assembling Chemical Libraries
    Item type: Journal Article
    Melkko, Samu; Sobek, Jens; Guarda, Greta; et al. (2005)
    Chimia
Publications 1 - 10 of 90