Identifizierung der Rezeptorinteraktion von RF-amid-Peptiden auf molekularer Ebene

• Applicant: Professorin Dr. Annette G. Beck-Sickinger
• Subject Area: Biochemistry
• Term: from 2007 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 52261075

RF-amide-peptides consist of 8-26 amino acids in human and contain C-terminally a characteristic Arg-Phe-amide-dipeptide motif. Six RF-amide-peptides have been described in human. For the last two years this peptide family has gained significant interest mainly because of its pharmacologically important activities like modulation of pain, stress control, regulation of day/night rhythm and food intake. The peptides bind to 4 receptors in human that all belong to the family of G-protein coupled receptors. We recently could identify the ligand binding site of neuropeptide Y and based on these data we hypothesize a strong ionic and important interaction of the conserved Arg residue of the RF-amide peptides with residue Asp6.59 of the correspondent receptor. We plan to use synthetic peptide analogues, receptor mutagenesis and complementary interaction studies to identify the ligand binding pocket on a molecular level. This might contribute significantly to the overall understanding of binding and signal transduction of peptides that interact with GPCRs. Furthermore, our data could support drug development in these systems and clarify the important problem of ligand selectivity of RF-amide peptides. Owing to the evolutionary old family of RF-amide peptides we might contribute to a better understanding of the coevolution of ligands and receptors.

• DFG Programme: Research Grants