Research and Publications

Selected publications:

Muratspahić E., Deibler K., Han J. et al. Design and structural validation of peptide–drug conjugate ligands of the kappa-opioid receptor. Nature Communications 14, 8064 (2023).

Tomašević N., Emser F.S., Muratspahić E., Gattringer J., Hasinger S., Hellinger R., Keov P., Felkl M., Gertsch J., Becker C.F.W., Gruber C.W. Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor. Journal of Biological Chemistry (2024), DOI: 10.1016/j.jbc.2024.107330

Thell K., Hellinger R., Sahin E., Michenthaler P., Gold-Binder M., Haider T., Kuttke M., Liutkevičiūtė Z., Göransson U., Gründemann C., Schabbauer G., Gruber C.W. Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis. Proceedings of the National Academy of Sciences USA 113(15):3960-5 (2016).

Muratspahić E., Tomašević N., Koehbach J., Duerrauer L., Hadžić S., Castro J., Schober G., Sideromenos S., Clark R.J., Brierley S.M., Craik D.J. & Gruber C.W. Design of a stable cyclic peptide analgesic derived from sunflower seeds that targets the κ-opioid receptor for the treatment of chronic abdominal pain. Journal of Medinical Chemistry 64(13):9042-9055 (2021).

Hellinger R., Sigurdsson A., Wu W., Romanova E.V., Li L., Sweedler J.V., Süssmuth R.D. & Gruber C.W. Peptidomics. Nature Reviews Methods Primers 3, 25 (2023).

For a full list of publications, please refer to PubMed or GoolgleScholar.

GPCR molecular pharmacology and drug discovery

Starting from nature-derived scaffolds, such as macrocyclized plant peptides or stabilized neuropeptide analogs found in animals, we use computational tools or peptide chemistry approaches to design novel peptide ligands of G protein-coupled receptors (GPCRs) – focusing on oxytocin/vasopressin- & opioid-receptors – to explore their molecular signaling properties, structural details of the ligand/receptor interaction and explore biomedical applications to identify possible therapeutics for pain or autoimmune disorders, including multiple sclerosis and inflammatory bowel disorders.

Discovery and function of nature-derived peptides

Utilizing state-of-the-art mass spectrometry combined with genome/transcriptome mining we isolate peptides from diverse sources, including plants (knottins, cyclotides and AMPs), insects (neuropeptides and AMPs) and venomous animals (conotoxins), analyze their structural diversity and enzymatic biosynthesis, and explore their biological function and application as enzyme inhibitors, ligands of GPCRs and modulators of immune function.

Comparative neuropeptide physiology and pharmacology

Using ants and their endogenous inotocin (oxytocin/vasopressin-like) signaling system, we explore neuropeptide signaling in insects to gain novel insights into their function. Utilizing computational biology and comparative pharmacology we study the molecular details of the human peptide/receptor systems to advance our understanding of GPCR signaling.