ANALYSIS OF C3D/EBV RECEPTOR (CR2) LIGAND BINDING SITES

我们正在寻求资金，以确定和表征配体结合 人补体受体2（CR2）上的C3 d，g位点和 EB病毒（EBV），使用基于肽的方法。 初步 实验利用重组DNA为基础的方法，我们有 将这些位点定位在受体的亚结构域上。 我们正在扩展 这些重组研究进一步定位关键结构域和氨基 酸通过定点诱变、同源扫描诱变来移动 小鼠CR2序列到人CR2上，以及构建可溶性 CR2的重组形式。 我们在此提议并正在寻求资金， 合成将被测试的CR2衍生肽或其 抑制C3 d，g和EBV结合。 在初步查明 相关肽，我们将尝试合成衍生物， 增强活动。 通过这种受体-配体的协调方法 互动分析，预计广泛的了解， 这些网站将获得。 这一理解将进一步 免疫治疗的实验性和可能更好的临床方法， 通过CR2介导的抗病毒治疗。

We are seeking funding to identify and characterize the ligand binding sites on human Complement Receptor 2 (CR2) for C3d,g and the Epstein-Barr virus (EBV) using a peptide based pproach. In preliminary experiments utilizing a recombinant DNA based approach, we have localized these sites to a sub-domain of the receptor. We are extending these recombinant studies to further localize critical domains and amino acids by site-directed mutagenesis, homolog-scanning mutagenesis to move mouse CR2 sequence onto human CR2, and construction of soluble recombinant forms of CR2. We propose herein and are seeking funding to synthesize CR2 derived peptides which will be tested or their ability to inhibit C3d,g and EBV binding. Following initial identification of relevant peptides, we will attempt to synthesize derivatives with enhanced activity. Through this coordinated approach to receptor-ligand interaction analysis, it is anticipated that an extensive understanding of these sites will be obtained. This understanding will allow further experimental and perhaps better clinical approaches to immunotherapy and anti-viral therapy mediated through CR2.