| RRC ID |
58720
|
| 著者 |
Kadonosono T, Yimchuen W, Ota Y, See K, Furuta T, Shiozawa T, Kitazawa M, Goto Y, Patil A, Kuchimaru T, Kizaka-Kondoh S.
|
| タイトル |
Design Strategy to Create Antibody Mimetics Harbouring Immobilised Complementarity Determining Region Peptides for Practical Use.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Monoclonal antibodies (mAbs) are attractive therapeutics for treating a wide range of human disorders, and bind to the antigen through their complementarity-determining regions (CDRs). Small stable proteins containing structurally retained CDRs are promising alternatives to mAbs. In this report, we present a method to create such proteins, named fluctuation-regulated affinity proteins (FLAPs). Thirteen graft acceptor (GA) sites that efficiently immobilise the grafted peptide structure were initially selected from six small protein scaffolds by computational identification. Five CDR peptides extracted by binding energy calculations from mAbs against breast cancer marker human epithelial growth factor receptor type 2 (HER2) were then grafted to the selected scaffolds. The combination of five CDR peptides and 13 GA sites in six scaffolds revealed that three of the 65 combinations showed specific binding to HER2 with dissociation constants (KD) of 270-350 nM in biolayer interferometry and 24-65 nM in ELISA. The FLAPs specifically detected HER2-overexpressing cancer cells. Thus, the present strategy is a promising and practical method for developing small antibody mimetics.
|
| 巻・号 |
10(1)
|
| ページ |
891
|
| 公開日 |
2020-1-21
|
| DOI |
10.1038/s41598-020-57713-4
|
| PII |
10.1038/s41598-020-57713-4
|
| PMID |
31964960
|
| PMC |
PMC6972867
|
| MeSH |
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal, Humanized / chemistry
Antibodies, Monoclonal, Humanized / genetics
Antibodies, Monoclonal, Humanized / metabolism
Antigens / metabolism
Cell Line, Tumor
Complementarity Determining Regions / genetics
Complementarity Determining Regions / immunology*
Drug Design
Epitopes / metabolism
HeLa Cells
Humans
Molecular Dynamics Simulation
Protein Engineering / methods*
Receptor, ErbB-2 / genetics
Receptor, ErbB-2 / immunology
Receptor, ErbB-2 / metabolism*
Recombinant Proteins / genetics
Recombinant Proteins / immunology*
Recombinant Proteins / metabolism*
Reproducibility of Results
Stomach Neoplasms / immunology
Stomach Neoplasms / metabolism
Trastuzumab / chemistry
Trastuzumab / genetics
Trastuzumab / metabolism
|
| IF |
3.998
|
| 引用数 |
0
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa |
