CHRISTIAN GRUBER

speaker

CHRISTIAN GRUBER

Center for Physiology and Pharmacology at the Medical University of Vienna (Austria)

Neuropeptides, crucial for human health and disease, act primarily via G protein-coupled receptors (GPCRs), the largest family of cell surface receptors in the human genome. Despite their therapeutic potential, peptide drugs targeting GPCRs face challenges such as poor pharmacokinetics due to rapid degradation. To address this issue, we explore genomes/transcriptomes in combination with peptidomics of plants, invertebrates and venomous animals to identify evolutionary-related human neuropeptide analogues. Using innovative chemical and computational approaches, including molecular grafting, backbone cyclization, cysteine stapling, and de novo design, we focus on developing stable, receptor-selective ligands with functional bias. These nature-derived peptides and their synthetic analogues exhibit promising pharmacological properties, offering potential for GPCR ligands with reduced off-target effects and enhanced stability, while serving as valuable chemical probes to deepen our understanding of molecular GPCR signalling.