Novel agonists and antogonists of chemokine receptors

DESCRIPTION (provided by the applicant): A key event in the initiation and maintenance of an inflammatory response is the recruitment of immune effector cells to the site of a local immune response. This recruitment and retention is mediated by chemoattractant compounds, of which chemokines are an essential component. The chemokine family consists of ~50 small proteins, which mediate effects through G-protein coupled chemokine receptors expressed on target cells.The long term objective of this study is to isolate and characterize effectors which regulate the chemokine / chemokine receptor interaction. To achieve this our phase I objective was to develop a Xenopus oocyte assay to identify and isolate novel peptidyl agonists / antagonists of the chemokine receptors. In phase I feasibility studies we developed an assay using the CCR3 receptor, and the chemokine eotaxin as a positive control. We also developed a peptide expression system, and initiated library screening.In phase II studies we propose to extend our assay development to all known chemokine receptors, and to characterize the agonist and antagonist effectors isolated in our assay. The results of these studies will be used in the next phase of research, the development of lead compounds