Adaptor Protein-Quantum Dot Conjugates as Biological Labels

描述（由申请人提供）：NIH SBIR项目旨在开发三嵌段共聚物包被量子点（QD）和接头蛋白G片段生物偶联物作为生物医学应用的荧光探针。该项目的策略和设计基于我们最近在两亲性三嵌段聚合物包被量子点的合成和稳定，纳米晶体抗体偶联以及目标特异性体内成像方面的成功。目前商品化的QD抗体采用化学还原抗体（Ab）偶联到QD表面。与使用天然全抗体相比，修饰抗体与目标抗原的亲和力和特异性显著下降。在另一种流行的偶联化学中，抗体使用碳二亚胺与量子点连接。然而，抗体在量子点表面的取向是随机的，这不利于抗体的活性和特异性。第一期的成功开发将提供一种具有强亲和力和优越稳定性的小尺寸QD轴承万向连接器。对于学术和制药科学家以及医务工作者来说，这种蛋白质G/QD将具有成本效益。在第二阶段，将优化工艺，开发一系列具有不同发射颜色的承载万向链接的QD。所提出的蛋白质G-QD偶联物可以通过标准程序为特异性抗体的偶联提供灵活的解决方案。最终产品将包括具有不同发射颜色的蛋白G片段修饰量子点，共轭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/壳量子点；2)蛋白G/QD偶联物的制备；3)蛋白质G/QD偶联物的评价。美国国立卫生研究院SBIR项目旨在为生物医学应用提供一种新的生物偶联物作为荧光探针。与目前的商业产品相比，这种生物偶联物对学术和制药科学家以及医务工作者来说更有效、更可靠、更经济。

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.