Chemical Synthesis of Proteins Containing 300 Amino Acids

Chemical Synthesis of Proteins Containing 300 Amino Acids
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含 300 种氨基酸的蛋白质的化学合成

DOI:
10.1007/s40242-020-0150-y
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发表时间:
2020-06
影响因子:
3.1
通讯作者:
Liu Lei
Liu Lei
中科院分区:
化学3区
文献类型:
--
作者:
Zhang Baochang;Li Yulei;Shi Weiwei;Wang Tongyue;Zhang Feng;Liu Lei

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化学合成含有多达300个氨基酸的蛋白质可以覆盖生物医学研究中遇到的所有蛋白质的30%-50%,并且可以提供通常使用的重组表达技术的替代方法,极大地扩展了后者的化学空间。本文综述了近年来在快速合成越来越长的多肽和高效连接多个多肽片段方面取得的进展。许多研究小组的开创性方法的发展极大地促进了许多功能重要蛋白质的成功全合成的最新突破,如寡-biquitins,细菌GroEL/ES分子伴侣和镜像DNA聚合酶。通过这些研究,也认识到化学合成大蛋白质的潜在瓶颈,即如何确保来自大蛋白质的每个肽段在溶解于水溶液中时避免不利的聚集。许多新的方法,如可移除骨架修饰(RBM)策略已经被开发出来以克服这一瓶颈,同时需要进行更多的研究来开发更有效和成本更低的方法,最终可能导致完全自动化的化学合成具有任何人工设计的300个氨基酸的定制蛋白。
Chemical synthesis of proteins containing up to 300 amino acids may cover 30%―50% of all the proteins encountered in biomedical studies and may provide an alternate approach to the usually used recombinant expression technology, vastly expanding the chemical space of the latter. In the present review article, we tried to survey the re-cent progresses made for more rapid synthesis of increasingly long peptides and more efficient ligation of multiple peptide segments. The developments of seminal methods by many research groups have greatly contributed to the recent breakthroughs in the successful total synthesis of a number of functionally important proteins, such as oligou-biquitins, bacterial GroEL/ES chaperones, and mirror-image DNA polymerases. Through these studies, a potential bottleneck has also been recognized for the chemical synthesis of large proteins, namely, how to ensure that each peptide segment from a large protein avoids unfavorable aggregation when dissolved in aqueous solution. Many new methods, such as removable backbone modification(RBM) strategy have been developed to overcome this bottleneck, while more studies need to be carried out to develop more effective and less costly methods that ultimately, may lead to fully automatable chemical synthesis of customized proteins of 300 amino acids bearing any artificial designs.
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