What we do:
The Gmeiner research lab operates at the multidisciplinary interface of synthetic organic chemistry, medicinal chemistry, chemical biology, and structural biology. The core mission of the laboratory is to discover novel probes and drug candidates for G protein-coupled receptors (GPCRs) and other challenging membrane proteins, contributing significantly to the development of highly attractive CNS-active drugs.
The group’s scientific activities are structured around four interconnected pillars:
- Structure-Based Drug Design & Synthesis: Utilizing atomic-resolution blueprints determined by cryogenic electron microscopy (cryo-EM), the lab investigates the design, organic synthesis, and pharmacological properties of bioactive molecules, focusing particularly on biogenic amine analogs and peptide mimetics to explore new chemical spaces.
- Functional Selectivity & Intrinsic Activity: Through advanced functional assays, the group exploits receptor structural plasticity to achieve biased signaling. This approach reveals the molecular origins of intrinsic activity, allowing the design of next-generation therapeutics that decouple therapeutic efficacy from adverse side effects.
- Allosteric Modulation & Subtype Selectivity: To achieve absolute subtype selectivity within highly conserved receptor families, the team combines radioligand binding studies with the exploration of less-conserved allosteric topography, expanding these concepts into custom-tailored polypharmacology for multi-factorial diseases.
- Chemical Biology & Molecular Probes: The laboratory designs sophisticated molecular tools to visualize and manipulate receptor dynamics in real time, including photoswitchable ligands for photopharmacology, fluorescent probes for single-molecule microscopy, and target-specific radioligands for molecular imaging and theranostics.
