Chemical methods for peptide and protein production.

Chemical methods for peptide and protein production.
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肽和蛋白质产生的化学方法。

DOI:
10.3390/molecules18044373
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发表时间:
2013-04-12
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Toth I
Toth I
中科院分区:
其他
文献类型:
--
作者:
Chandrudu S;Simerska P;Toth I

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自1963年梅里菲尔德发明固相合成方法以来,专注于肽合成的研究小组数量呈指数级增长。然而,最初的分步合成具有局限性:最终产物的纯度随着偶联步骤的数量而降低。继Boc和Fmoc保护基的发展之后,新的氨基酸保护基和新的技术被引入,以提供高质量和数量的肽产品。片段缩合是20世纪80年代流行的肽生产方法,但不幸的是,外消旋化速率和反应难度证明不太理想。肯特及其同事通过引入未保护肽的化学选择性反应(称为天然化学连接),彻底改变了肽偶联。随后,研究集中在新的连接技术的发展,包括著名的点击反应,肽酰肼的连接,以及最近报道的α-酮酸-羟胺与5-氧脯氨酸的连接。世界各地已经成立了几家公司,以制备多公斤规模的高质量良好生产规范肽产品。本文综述了多肽化学的研究进展,包括目前合成多肽的各种方法以及多肽在药物化学中的广泛应用。
Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported α-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.
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