Employees – University of Copenhagen

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Department of Drug Design and Pharmacology > Employees

Maria Damgaard

Maria Damgaard

PhD fellow

Current research

γ-Hydroxybutyric (GHB) acid is a neuromodulator working alongside the main inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain. The neuropharmacology of GHB is complex and involves both low- and high-affinity binding sites. Two positive allosteric modulators (PAMs) of the GHB high affinity binding have been identified in a small library screen.

This project intend to clarify the localization and architecture of the binding sites for the identified PAMs, using medicinal chemistry efforts including an elaborate structure-activity study (SAR) in combination with reliable homology receptor models and labeling studies.

The described medicinal chemistry project will be part of an iterative process in close interaction with computational modeling and molecular pharmacology aspects of the overall project, and will include:

  • Structure-activity studies (SAR.) Synthesis strategies will be developed for both compounds. Series of compounds, designed by systematic deconstruction of the lead compounds, will be synthesized focusing on different parts of the two scaffolds with the intention of simplifying the structures and mapping the pharmacophoric features for activity, potency and selectivity.
  • Development of labeling ligands. Synthesis strategies will be developed enabling introduction of labels such as radioactivity, fluorescent and photoaffinity groups.
  • Development of ligands for in vivo animal studies and potential drug candidates. To obtain blood brain penetration and stability for use in in vivo studies, pharmacokinetic properties will be studied and optimized.

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