靶向Siglec-2的光敏性多功能糖簇分子的设计、合成与生物应用研究

涎免凝素(Siglecs)是一类重要的唾液酸结合性免疫球蛋白样凝集素家族。其中，Siglec-2限制性表达于成熟B细胞表面，被视为B细胞淋巴瘤的标志物，以其为靶向受体，可以发展抗肿瘤药物。目前有一些靶向Siglec-2的抗体进入临床用于治疗B细胞淋巴瘤，但是靶向抗体存在制备与纯化复杂，储存条件严苛，价格昂贵等问题。本项目在课题组多年糖化学生物学研究的基础上，设计与构建两种靶向Siglec-2、唾液酸寡糖修饰、水溶性、具有光敏活性的多功能糖簇分子。它们是以氮杂氟硼荧为荧光团的常亮型糖簇分子3GS-I，和以四苯乙烯-四氰基蒽醌缀合物为荧光团的点亮型糖簇分子3GS-II。研究其在模型鼠B细胞淋巴瘤诊断和光动力治疗中的潜在应用。本项目所设计合成的目标分子是一类具有潜在诊疗一体化应用前景的多功能糖簇分子，开展其研究将为B细胞淋巴瘤的诊断和治疗提供新的研究思路，具有重要的科学研究价值和广阔的应用前景。

Siglecs are a big family of sialic acid binding immunoglobulin-like lectins. Among them, Siglec-2 is over-expressed on the surface of mature B cells, and is considered as a marker of B cell lymphoma. Antitumor drugs can be developed with Siglec-2 as a targeted receptor. Till now, some antibodies targeting Siglec-2 have been used in clinical treatment of B-cell lymphoma. However, the preparation and purification of antibodies targeting Siglec-2 are complicated, the storage conditions are rigorous, and the price is expensive. In this project, we will design and synthesize two multifunctional glycoclusters targeting Siglec-2 with characteristics such as sialo-oligosaccharide modification, water-solublity and photosensitivity, and study their potential applications in B-cell lymphoma detection and photodynamic therapy in model mice. These two molecules are “always-on” glycocluster 3GS-I with aza-BODIPY as fluorophore, and “turn-on” glycocluster 3GS-II with tetraphenylethylene-tetracyanoanthraquinone conjugate as fluorophore. The target molecule designed and synthesized by this project is a kind of multifunctional glycocluster molecule which has potential application prospect in tumor diagnosis and treatment. The project will provide a new research idea for the diagnosis and treatment of B-cell lymphoma, which has important scientific research value and broad application prospects.