Detail

Keywords

Amino Acids, Peptides, and Proteins; Cyclotides; Molecular Pharmacology of Bioactive Peptides from Nature; Proteomics

Research group(s)

• Drug Discovery
  Head: Christian Gruber
  Research Area: Our main research interest is the study of molecular mechanisms in living organisms by employing a toolbox of nature-derived and synthetically optimized peptides with biological activity to be analyzed in vitro and in vivo. The research includes the isolation, structural characterization, design and synthesis of biologically active peptides, which will be useful for drug discovery or as molecular probes.
  Members:
  Christian Gruber
  Roland Hellinger

Research interests

My main research focus is to understand the importance of natural bioactive peptide from plants and their application to modulate molecular receptors and enzymes. The research is designed to elucidate molecular mechanisms of bioactive circular cystine-rich peptides such as immune system modulation and to understand the underlying effects. Natural bioactive peptide ligands are identified using a bioassay-guided fractionation and their structure-function and bioactivity-structure relationship are studied by applying chemical synthesis and activity assignments. Promising ligand peptideds are improved to provide future drug candidates.

Techniques, methods & infrastructure

Mass spectrometry based proteomics and peptidomics using MALDI-TOF/TOF-MS and LC-MS/MS; Peptide chemical Biology, G-protein coupled receptor pharmacology, Peptide Bioactivity-Structure relationship studies, Functional protein expression, protease inhibition assays.

Grants

• Psysol 2 is a novel modulator of human prolyl oligopeptidase (2023)
  Source of Funding: FWF (Austrian Science Fund), Stand Alone Project
  Principal Investigator
• PeptAIDEs - Peptide Therapeutics for Autoimmune and Inflammatory Diseases (2020)
  Source of Funding: FWF (Austrian Science Fund), Zukunftskollegs
  Coordinator of the collaborative project

Selected publications

1. Hellinger, R. et al. (2021) ‘Importance of the Cyclic Cystine Knot Structural Motif for Immunosuppressive Effects of Cyclotides’, ACS Chemical Biology, 16(11), pp. 2373–2386. Available at: http://dx.doi.org/10.1021/acschembio.1c00524.
2. Gattringer, J. et al. (2021) ‘Cyclotides Isolated From Violet Plants of Cameroon Are Inhibitors of Human Prolyl Oligopeptidase’, Frontiers in Pharmacology, 12. Available at: http://dx.doi.org/10.3389/fphar.2021.707596.
3. Hellinger, R. et al. (2017) ‘Chemical Proteomics for Target Discovery of Head-to-Tail Cyclized Mini-Proteins’, Frontiers in Chemistry, 5. Available at: http://dx.doi.org/10.3389/fchem.2017.00073.
4. Hellinger, R. et al. (2015) ‘Peptidomics of Circular Cysteine-Rich Plant Peptides: Analysis of the Diversity of Cyclotides from Viola tricolor by Transcriptome and Proteome Mining’, Journal of Proteome Research, 14(11), pp. 4851–4862. Available at: http://dx.doi.org/10.1021/acs.jproteome.5b00681.