Adaptor Protein-Quantum Dot Conjugates as Biological Labels

描述（由申请人提供）：该NIH SBIR计划旨在开发三嵌段共聚物包被的量子点（QD）和衔接蛋白G片段生物缀合物，作为生物医学应用的荧光探针。该项目的策略和设计是基于我们最近在两亲性三嵌段聚合物包覆的量子点的合成和稳定化、纳米抗体缀合物和靶向特异性体内成像方面的成功。目前商业化的抗体-QD使用化学还原的抗体（Ab）与QD表面缀合。与使用天然全抗体相比，修饰的抗体与靶抗原之间的亲和力和特异性显著下降。在另一种流行的缀合化学中，使用碳二亚胺将抗体连接到QD。然而，抗体在QD表面上的取向是随机的，这不利于抗体活性和特异性。阶段I的成功开发将提供具有强亲和力和上级稳定性的携带通用接头的小尺寸QD。这种蛋白质G/QD对于学术和制药科学家以及医务工作者来说将是具有成本效益的。在第二阶段，将优化工艺，并开发一系列具有不同发射颜色的QD轴承通用链接。所提出的蛋白质G-QD缀合物可以提供通过标准程序缀合特异性抗体的灵活解决方案。最终产品将包括具有不同发射颜色的蛋白G片段修饰的量子点、缀合方法和连接抗体的试剂，具体目标是：1）制备生物相容性和生物可连接的核/壳QD; 2）制备蛋白G/QD缀合物;和3）评价蛋白G/QD缀合物。该NIH SBIR计划旨在提供一种新的生物缀合物作为生物医学应用的荧光探针。与目前的商业产品相比，这种生物缀合物将更有效，更可靠，并且对于学术和制药科学家以及医务工作者来说是经济有效的。

DESCRIPTION (provided by applicant): This NIH SBIR program intends to develop triblock copolymer coated quantum dot (QD) and adaptor protein G fragment bioconjugates as fluorescent probes for biomedical applications. The strategy and design of this project are based on our recent success in the synthesis and stabilization of amphiphilic triblock polymer coated QDs, the nanocrystal-antibody conjugations, and the target specific in vivo imaging . The current commercial antibody-QD uses chemically reduced antibodies (Ab) to conjugate to QD surface. The affinity and specificity between the modified antibody and the targeted antigen drops substantially in comparison with that using native whole antibody. In another popular conjugation chemistry, antibodies are linked to QDs using carbodiimide. However the orientation of the Ab on QD surface is random, which is detrimental to Ab activity and specificity. Successful development of Phase I will provide a small-size QD bearing universal linker with strong affinity and superior stability. This protein G/QD will be cost efficient for academic and pharmaceutical scientists as well as medical workers. In Phase II, the process will be optimized and a series of QD bearing universal links with different emission colors will be developed. The proposed protein G-QD conjugates could provide flexible solutions to conjugate specific antibodies through standard procedures. The final products will include protein G fragment modified quantum dots with different emission colors, conjugate methods, and regents to link antibodies, the specific aims are: 1) preparation of biocompatible and biolinkable core/shell QDs; 2) preparation of protein G/QD conjugates; and 3) evaluation of protein G/QD conjugates. This NIH SBIR program intends to provide a new bioconjugate as fluorescent probe for biomedical applications. In comparison with the current commercial products, this bioconjugate will be more effective, more reliable, and cost efficient for academic and phamaceutical scientists as well as medical workers.