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minglinana银虫 (初入文坛)
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[求助]
抗体上赖氨酸的氨基进行药物偶联已有1人参与
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现在抗体上的赖氨酸残基上有氨基，对氨基进行药物偶联，现在求助较优的氨基偶联条件，或者谁手头上有相关的氨基偶联文献，还请各位大侠不吝赐教。 发自小木虫IOS客户端 |
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2楼2017-04-13 21:25:22
【答案】应助回帖
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http://html.rhhz.net/gfzxb/html/gfzxb20170204.htm 蛋白质-聚氨基酸偶联物的高效合成与应用 张冲 , 吕华 摘要：蛋白质-高分子偶联物是重要的临床药物，可用于多种疾病的治疗.寻找新的生物可降解高分子材料来替代传统的聚乙二醇和发展高效、位点特异性的偶联方法是该领域目前所面临的2个重要挑战.聚氨基酸是一类具有较好生物相容性、可生物降解、含有丰富侧链官能团的仿生功能高分子，在蛋白质修饰方面具有突出的优势，是有较大潜力的聚乙二醇替代物.本专论主要从新型α-氨基酸-N-羧基酸酐（N-carboxyanhydrides，NCA）可控开环聚合方法、聚氨基酸原位官能化制备位点特异性蛋白质偶联物、扩展功能聚氨基酸分子库调控蛋白质功能等3个方面详细介绍蛋白质-聚氨基酸领域的研究进展，并对这类新型偶联物的发展进行了简单的评述和展望. 关键词：蛋白质偶联物 聚氨基酸 模拟蛋白翻译后修饰 拓扑结构 刺激响应性 Efficient Synthesis and Application of Protein-Poly(α-amino acid) Conjugates Zhang Chong , Lu Hua Efficient Synthesis and Application of Protein-Poly(α-amino acid) Conjugates Zhang Chong , Lu Hua Abstract: 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(α-amino acid)s (PαAAs) 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-PαAAs conjugates. Specifically, we discuss our developments in: (1) Recent developments in the controlled ring-opening polymerization (ROP) of α-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 PαAAs 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 PαAAs, 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 PαAAs, 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-PαAA conjugates including the head-to-tail circular conjugates. (3) Development of functional PαAAs for potential protein conjugation. Various functional PαAAs have been developed as delivery materials or hydrogels. To further expand the arsenal of PαAAs for potential modulation of protein functions, PαAAs that mimic protein post-translational modifications (PTM) are synthesized; On the other hand, a series of multiple stimuli-responsive PαAAs are also produced. These PαAAs show interesting enzyme, light, and/or thermal responsiveness, which could be potentially harnessed for modulation of protein functions in the future. Key words: Protein conjugation Poly(α-amino acid) PTM mimicking Topology Stimuli-responsiveness |
3楼2020-06-22 11:16:43