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| Mechano-bioconjugation Strategy Empowering Fusion Protein Therapeutics with Aggregation Resistance, Prolonged Circulation, and Enhanced Antitumor Efficacy | |
| Liu, Yajie1; Bai, Xilin1; Lyu, Chengliang2; Fang, Jing1; Zhang, Fan1; Wu, Wen-Hao1; Wei, Wei2; Zhang, Wen-Bin1 | |
| 2022-09-30 | |
| Source Publication | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
 |
| ISSN | 0002-7863 |
| Pages | 10 |
| Abstract | Bioconjugation is a powerful protein modification strategy to improve protein properties. Herein, we report mechano-bioconjugation as a novel approach to empower fusion protein therapeutics and demonstrate its utility by a protein heterocatenane (cat-IFN-ABD) containing interferon-alpha 2b (IFN) mechanically interlocked with a consensus albumin-binding domain (ABD). The conjugate was selectively synthesized in cellulo following a cascade of post-translational events using a pair of heterodimerizing p53dim variants and two orthogonal split-intein reactions. The catenane topology was proven by combined techniques of LC-MS, SDS-PAGE, SEC, and controlled proteolytic digestion. Not only did caiIFN-ABD retain activities comparable to those of the wild-type IFN and ABD, the conjugate also exhibited enhanced aggregation resistance and prolonged circulation time over the simple linear and cyclic fusions. Consequently, cat-IFN-ABD potently inhibited tumor growth in the mouse xenograft model. Therefore, mechano-bioconjugation by catenation accomplishes function integration with additional benefits, providing an alternative pathway for developing advanced protein therapeutics. |
| DOI | 10.1021/jacs.2c06532 |
| Language | 英语 |
| WOS Keyword | ALBUMIN-BINDING DOMAIN ; HALF-LIFE EXTENSION ; ACCELERATED BLOOD CLEARANCE ; PHARMACOKINETICS ; STABILITY ; STABILIZATION ; INTERFERONS ; CONJUGATION ; PEGYLATION ; PEPTIDES |
| WOS Research Area | Chemistry |
| WOS Subject | Chemistry, Multidisciplinary |
| WOS ID | WOS:000865365100001 |
| Publisher | AMER CHEMICAL SOC |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ipe.ac.cn/handle/122111/54997 |
| Collection | 中国科学院过程工程研究所 |
| Corresponding Author | Wei, Wei; Zhang, Wen-Bin |
| Affiliation | 1.Peking Univ, Coll Chem & Mol Engn, Ctr Soft Matter Sci & Engn, Minist Educ,Beijing Natl Lab Mol Sci,Key Lab Polym, Beijing 100871, Peoples R China 2.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China |
| Recommended Citation GB/T 7714 | Liu, Yajie,Bai, Xilin,Lyu, Chengliang,et al. Mechano-bioconjugation Strategy Empowering Fusion Protein Therapeutics with Aggregation Resistance, Prolonged Circulation, and Enhanced Antitumor Efficacy[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2022:10. |
| APA | Liu, Yajie.,Bai, Xilin.,Lyu, Chengliang.,Fang, Jing.,Zhang, Fan.,...&Zhang, Wen-Bin.(2022).Mechano-bioconjugation Strategy Empowering Fusion Protein Therapeutics with Aggregation Resistance, Prolonged Circulation, and Enhanced Antitumor Efficacy.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,10. |
| MLA | Liu, Yajie,et al."Mechano-bioconjugation Strategy Empowering Fusion Protein Therapeutics with Aggregation Resistance, Prolonged Circulation, and Enhanced Antitumor Efficacy".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2022):10. |
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