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

rf -酰胺肽在人体中由8-26个氨基酸组成，其末端含有一个特征的精氨酸-苯胺-二肽基序。六种rf酰胺肽已在人体中被描述。在过去的两年中，这个肽家族获得了极大的兴趣，主要是因为它具有重要的药理学活性，如调节疼痛，压力控制，调节昼夜节律和食物摄入。这些肽与4种受体结合，这些受体都属于g蛋白偶联受体家族。我们最近可以确定神经肽Y的配体结合位点，并基于这些数据，我们假设rf酰胺肽的保守Arg残基与相应受体的残基Asp6.59之间存在强离子和重要的相互作用。我们计划利用合成肽类似物、受体诱变和互补相互作用研究在分子水平上鉴定配体结合袋。这可能有助于全面了解与gpcr相互作用的肽的结合和信号转导。此外，我们的数据可以支持这些系统中的药物开发，并澄清rf -酰胺肽配体选择性的重要问题。由于rf -酰胺肽的进化古老家族，我们可能有助于更好地理解配体和受体的共同进化。

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.