Artificial antibody created by conformational reconstruction of the complementary-determining region on gold nanoparticles.
Artificial antibody created by conformational reconstruction of the complementary-determining region on gold nanoparticles.
复制标题
通过金纳米粒子互补决定区构象重建产生的人工抗体
DOI：
10.1073/pnas.1713526115
复制
发表时间：
2018-01-02
影响因子：
11.1
通讯作者：
Cao A
中科院分区：
文献类型：
--
作者：
Yan GH;Wang K;Shao Z;Luo L;Song ZM;Chen J;Jin R;Deng X;Wang H;Cao Z;Liu Y;Cao A
模拟类似蛋白质的特定相互作用和功能一直是纳米技术长期追求的目标。关键的挑战是精确地将纳米颗粒上的非功能表面基团组织成特定的3D构象，以协调和编排的方式发挥作用。在这里，我们开发了一种方法，将天然抗体的互补决定区域移植到纳米颗粒上，并重建其“活性”构象，以创建基于纳米颗粒的人工抗体，以识别相应的抗原。我们的工作表明，可以通过构象工程在纳米颗粒上创建功能，即将柔性表面基团调整为特定的构象。我们直截了当的策略可以进一步用于创建其他各种应用的人工抗体，并为了解天然蛋白质的结构和折叠提供了新的工具。为了赋予纳米颗粒（NPs）生物医学功能，常用的方法是借助这些基团本身的功能将官能团共轭到NPs上。通过对NPs上的非官能团进行构象工程，在NPs上产生类似蛋白质的特异性相互作用和功能，目前还无法实现。在这里，我们开发了一种构象工程方法，通过对天然抗体在金NPs （AuNPs）上的互补决定区（cdr）进行构象重建，创建了一种基于np的人工抗体，称为“Goldbody”。CDR环在自由形式下是灵活和无功能的，控制其构象似乎是不可逾越的任务，却意外地以一种简单的方式完成了。在将游离CDR环的两个末端锚定在AuNPs上后，我们通过调整两个末端之间的跨度，成功地重建了CDR环的“活性”构象，结果，在AuNPs上成功地重建了原始特异性。利用该方法制备了两个特异性结合蛋清溶菌酶和表皮生长因子受体的金体，其明显的亲和力比原始天然抗体强几个数量级。我们的工作表明，有可能以类似蛋白质的方式在NPs上创建类似蛋白质的功能，即通过将柔性表面基团调整到正确的构象。鉴于金小体的明显优点，包括良好的稳定性，我们预计一类金小体可以针对不同的抗原被创造出来，从而在各种应用中作为天然抗体的替代品。
Mimicking protein-like specific interactions and functions has been a long-pursued goal in nanotechnology. The key challenge is to precisely organize nonfunctional surface groups on nanoparticles into specific 3D conformations to function in a concerted and orchestrated manner. Here, we develop a method to graft the complementary-determining regions of natural antibodies onto nanoparticles and reconstruct their “active” conformation to create nanoparticle-based artificial antibodies that recognize the corresponding antigens. Our work demonstrates that it is possible to create functions on nanoparticles by conformational engineering, namely tuning flexible surface groups into specific conformations. Our straightforward strategy could be used further to create other artificial antibodies for various applications and provides a new tool to understand the structure and folding of natural proteins. To impart biomedical functions to nanoparticles (NPs), the common approach is to conjugate functional groups onto NPs by dint of the functions of those groups per se. It is still beyond current reach to create protein-like specific interactions and functions on NPs by conformational engineering of nonfunctional groups on NPs. Here, we develop a conformational engineering method to create an NP-based artificial antibody, denoted “Goldbody,” through conformational reconstruction of the complementary-determining regions (CDRs) of natural antibodies on gold NPs (AuNPs). The seemingly insurmountable task of controlling the conformation of the CDR loops, which are flexible and nonfunctional in the free form, was accomplished unexpectedly in a simple way. Upon anchoring both terminals of the free CDR loops on AuNPs, we managed to reconstruct the “active” conformation of the CDR loops by tuning the span between the two terminals and, as a result, the original specificity was successfully reconstructed on the AuNPs. Two Goldbodies have been created by this strategy to specifically bind with hen egg white lysozyme and epidermal growth factor receptor, with apparent affinities several orders of magnitude stronger than that of the original natural antibodies. Our work demonstrates that it is possible to create protein-like functions on NPs in a protein-like way, namely by tuning flexible surface groups to the correct conformation. Given the apparent merits, including good stability, of Goldbodies, we anticipate that a category of Goldbodies could be created to target different antigens and thus used as substitutes for natural antibodies in various applications.
登录
查看更多内容
影响因子：
64.8
作者：
Bhardwaj, Gaurav;Mulligan, Vikram Khipple;Bahl, Christopher D.;Gilmore, Jason M.;Harvey, Peta J.;Cheneval, Olivier;Buchko, Garry W.;Pulavarti, Surya V. S. R. K.;Kaas, Quentin;Eletsky, Alexander;Huang, Po-Ssu;Johnsen, William A.;Greisen, Per Jr;Rocklin, Gabriel J.;Song, Yifan;Linsky, Thomas W.;Watkins, Andrew;Rettie, Stephen A.;Xu, Xianzhong;Carter, Lauren P.;Bonneau, Richard;Olson, James M.;Coutsias, Evangelos;Correnti, Colin E.;Szyperski, Thomas;Craik, David J.;Baker, David
通讯作者：
Baker, David
用于细胞成像的二氧化硅纳米颗粒中封装的增强型绿色荧光蛋白
影响因子：
6.7
作者：
Cai, Zhengwei;Ye, Zhangmei;Cao, Aoneng
通讯作者：
Cao, Aoneng
影响因子：
2.9
作者：
Lafont, Virginie;Schaefer, Michael;Dejaegere, Annick
通讯作者：
Dejaegere, Annick
影响因子：
7.4
作者：
Haiss, Wolfgang;Thanh, Nguyen T. K.;Fernig, David G.
通讯作者：
Fernig, David G.
DOI：
10.1073/pnas.0601755103
发表时间：
2006-04-18
影响因子：
11.1
作者：
Farokhzad, OC;Cheng, JJ;Langer, R
通讯作者：
Langer, R