| Title | Artificial antibody created by conformational reconstruction of the complementary-determining region on gold nanoparticles |
| Authors | Yan, Gui-Hua Wang, Kun Shao, Zhuxue Luo, Lei Song, Zheng-Mei Chen, Jingqi Jin, Rong Deng, Xiaoyong Wang, Haifang Cao, Zhonglian Liu, Yuanfang Cao, Aoneng |
| Affiliation | Shanghai Univ, Inst Nanochem & Nanobiol, Shanghai 200444, Peoples R China. Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China. Peking Univ, Beijing Natl Lab Mol Sci, Coll Chem & Mol Engn, Beijing 100871, Peoples R China. |
| Keywords | artificial antibody conformation engineering nanoparticle Goldbody EGFR DE-NOVO DESIGN RIBONUCLEASE-A HOT-SPOTS IN-VIVO PROTEIN CANCER RECEPTOR THERAPY COMPLEX BINDING |
| Issue Date | 2018 |
| Publisher | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |
| Citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2018, 115(1), E34-E43. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/500057 |
| ISSN | 0027-8424 |
| DOI | 10.1073/pnas.1713526115 |
| Indexed | SCI(E) |
| Appears in Collections: | å å¦ä¸ å å å·¥ç¨ å¦é ¢ |
