Wang Jinhai, Norcross Michael
Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Drug Discov Today. 2008 Jul;13(13-14):625-32. doi: 10.1016/j.drudis.2008.04.004. Epub 2008 Jun 3.
Chemokine receptors control and mediate a diverse array of physiological and pathogenic processes. Many seven transmembrane (TM) G-protein-coupled receptors (GPCRs), including chemokine receptors, exist as homo- or heterodimers. Growing evidence indicates that the dimeric form is the basic functional structure of these receptors. Hetero-dimerization may allow for enhanced or specific functions of receptors and may be essential for receptor activity. Thus, dimers may provide new targets for chemokine receptor-based therapies. Synthetic peptides of TM regions of chemokine receptors may interfere with homologous interactions and inhibit functional activity of the receptors. Therefore, TM peptides and possibly compounds that target dimers and/or signaling of chemokine receptors may have therapeutic applications.
趋化因子受体控制并介导一系列不同的生理和致病过程。许多七跨膜(TM)G蛋白偶联受体(GPCR),包括趋化因子受体,以同二聚体或异二聚体形式存在。越来越多的证据表明,二聚体形式是这些受体的基本功能结构。异源二聚化可能会增强受体的功能或赋予其特定功能,并且可能对受体活性至关重要。因此,二聚体可能为基于趋化因子受体的疗法提供新的靶点。趋化因子受体TM区域的合成肽可能会干扰同源相互作用并抑制受体的功能活性。因此,TM肽以及可能靶向趋化因子受体二聚体和/或信号传导的化合物可能具有治疗应用价值。