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覆量子点(QD)和适配器蛋白G片段生物偶联物，作为生物医学应用的荧光探针。这个项目的战略和设计是基于我们最近在两亲三嵌段聚合物包覆的量子点、纳米晶体-抗体结合物和靶向体内成像方面的成功合成和稳定。目前的商品化抗体QD使用化学还原抗体(Ab)与QD表面偶联。与天然全抗体相比，修饰后的抗体与靶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相连。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。一期的成功开发将提供一种亲和力强、稳定性好的小尺寸QD轴承万能连接件。这种G/QD蛋白对学术和制药科学家以及医务人员来说都是具有成本效益的。在第二阶段，将优化工艺，开发一系列不同排放颜色的QD轴承万向节。建议的蛋白G-QD偶联物可以通过标准程序提供灵活的解决方案来偶联特定的抗体。最终产品将包括不同发光颜色、不同偶联方法和不同试剂的蛋白G片段修饰的量子点，其具体目的是：1)制备生物相容和可生物链接的核/壳量子点；2)制备蛋白G/QD偶联物；3)对蛋白G/QD偶联物进行评价。这项NIH SBIR计划旨在提供一种新的生物偶联物作为生物医学应用的荧光探针。与目前的商业产品相比，对于学术和医药科学家以及医务工作者来说，这种生物结合物将更有效、更可靠、更具成本效益。

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.