Efficient Synthesis and Application of Protein-Poly(alpha-amino acid) Conjugates
文献类型：期刊论文
| 作者 | Zhang, Chong; Lu, Hua |
| 刊名 | ACTA POLYMERICA SINICA
 |
| 出版日期 | 2018 |
| 期号 | 1页码:21-31 |
| 关键词 | Protein Conjugation Poly(Alpha-amino Acid) Ptm Mimicking Topology Stimuli-responsiveness |
| ISSN号 | 1000-3304 |
| DOI | 10.11777/j.issn1000-3304.2018.17204 |
| 英文摘要 | Protein-polymer conjugates are important therapeutics for various diseases. There are currently two major challenges in this field: one is the search of new biodegradable polymers beyond traditional PEGylation, and the other is to develop highly efficient and site-specific conjugation strategy. Poly(alpha-amino acid)s (P alpha AAs) are biodegradable and biocompatible polymers with tunable properties and numerous functions, making them promising candidates for protein modification. In this review, we summarize our recent progresses in protein-P alpha AAs conjugates. Specifically, we discuss our developments in: (1) Recent developments in the controlled ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydrides (NCAs), including amine-based initiators, organometallic initiators, organosilicon amines initiators and sulfide-based initiators. For instance, trimethylsilyl phenylsulfide (PhSTMS) is a novel initiator for controlled ROP of NCAs. It exhibits higher nucleophilicity than conventional amine-based initiator, and thus affords considerably higher chain initiation rate to ensure a more controlled polymerization. Moreover, this initiator is well-tolerated to various functional groups. (2) In situ functionalization of P alpha AAs for site-specific protein conjugation, and construction of various topological structures. Using PhSTMS initiator, it in situ generates a reactive phenyl thioester group at one end of the P alpha AAs, which can be used for protein N-terminus conjugation via native chemical ligation (NCL); moreover, ROP of glycine NCA yields oligoglycine at the other end of P alpha AAs, which can be used for C-terminus protein conjugation via sortase-A mediated ligation (SML). More interestingly, combinatory use of the two methods can construct various topological protein-P alpha AA conjugates including the head-to-tail circular conjugates. (3) Development of functional P alpha AAs for potential protein conjugation. Various functional P alpha AAs have been developed as delivery materials or hydrogels. To further expand the arsenal of P alpha AAs for potential modulation of protein functions, P alpha AAs that mimic protein post-translational modifications (PTM) are synthesized; On the other hand, a series of multiple stimuli-responsive P alpha AAs are also produced. These P alpha AAs show interesting enzyme, light, and/or thermal responsiveness, which could be potentially harnessed for modulation of protein functions in the future. |
| 语种 | 英语 |
| WOS记录号 | WOS:000429058600003 |
| 出版者 | SCIENCE PRESS |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/45939]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Lu, Hua |
| 作者单位 | Peking Univ, Beijing Natl Lab Mol Sci, Key Lab Polymer Chem & Phys, Minist Educ,Ctr Soft Matter Sci & Engn,Coll Chem, Beijing 100871, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Chong,Lu, Hua. Efficient Synthesis and Application of Protein-Poly(alpha-amino acid) Conjugates[J]. ACTA POLYMERICA SINICA,2018(1):21-31. |
| APA | Zhang, Chong,&Lu, Hua.(2018).Efficient Synthesis and Application of Protein-Poly(alpha-amino acid) Conjugates.ACTA POLYMERICA SINICA(1),21-31. |
| MLA | Zhang, Chong,et al."Efficient Synthesis and Application of Protein-Poly(alpha-amino acid) Conjugates".ACTA POLYMERICA SINICA .1(2018):21-31. |
入库方式： OAI收割
来源：化学研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。