Universität Leipzig

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Research data repository of Leipzig University.

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Browsing Universität Leipzig by Author "Beck-Sickinger, Annette G."

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  • ItemOpen Access
    Dataset for "NanoBRET-based detection of ligand-receptor interactions at the neuropeptide FF receptor 1" V2
    (Universität Leipzig, 2026-04-14) Lentschat, Hannah; Beck-Sickinger, Annette G.
    The neuropeptide FF receptor 1 (NPFFR1) belongs to the RF-amide G protein-coupled receptor family. Even though it is a promising therapeutic target for the treatment of chronic pain, this receptor still has not been used as a drug target. A detailed understanding of its ligand-binding and activation mechanisms is essential for the rational design of novel modulators. In this study, we developed a non-radioactive, nanoBRET-based ligand-binding assay to investigate ligand interactions of neuropeptide FF (NPFF) and neuropeptide VF (NPVF) with the NPFFR1. Fluorescently labeled NPFF and NPVF analogs were synthesized by conjugating a 6-carboxytetramethylrhodamine fluorophore at distinct positions, while a nanoluciferase was fused to the N-terminus of the NPFFR1 to serve as the BRET donor. This approach enables quantitative measurement of ligand binding and provides insights into the relative orientation of the ligand and receptor. Distinct BRET signal profiles for NPFF and NPVF, with a smaller window for NPVF compared to NPFF when directly labeled with the fluorophore, indicate differences in the binding orientation. Furthermore, deletion of the N-terminal residues of the receptor revealed that this region is dispensable for ligand recognition and binding in the NPFFR1. The assay was confirmed for small molecule NPFFR1 ligands, such as hederagenin, offers new opportunities to explore subtype selectivity and will guide drug discovery targeting the RF-amide receptor family.
  • ItemOpen Access
    Dataset for "Targeted, receptor-mediated delivery of a masked ᴅ-amino acid cell penetrating peptide for cell-specific phototoxicity"
    (Universität Leipzig, 2025-11-06) List, Moritz; Jülke, Eva-Maria; Beck-Sickinger, Annette G.
    Photodynamic therapy is an innovative treatment option for cancer, but current approaches are limited by poor tumor selectivity and low uptake. Here, we introduce a novel concept for a targeted phototoxic peptide, in which a lysosomally activatable payload is delivered selectively by receptor-mediated endocytosis. For the payload, 6-carboxytetramethylrhodamine (TMR) was attached to an activatable cell penetrating peptide. The regular activity of the CPP was blocked by electrostatic interactions with a poly-glutamate sequence but could be restored through cleavage by the lysosomal protease cathepsin B both in vitro and in cells. The unmasked CPP can then bind to the negatively charged lysosomal membrane, and upon irradiation, TMR generates reactive oxygen species (ROS) that disrupt the integrity of the membrane. This leads to a release of lysosomal contents into the cytosol which subsequently induces cell death. To achieve targeted delivery, the activatable payload was conjugated to chemerin-9, a high-affinity ligand for the chemokine-like receptor 1 (CMKLR1), a G protein-coupled receptor overexpressed in various cancers. Through this receptor-targeted approach, the peptide accumulates in CMKLR1-expressing cells while the lysosomal activation completely prevented off-target toxicity. Notably, this strategy enables even a weak photosensitizer like TMR to achieve potent cytotoxicity through lysosomal targeting. This approach represents an advancement in improving the selectivity and efficacy of photodynamic therapy and holds promise for the development of novel cancer therapies. Furthermore, the concept opens possibilities for specific intracellular delivery of peptides or proteins.