Peptides as drugs: Is there a market?
Peptides as drugs: Is there a market?
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DOI：
10.1002/psc.366
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发表时间：
2002-01-01
影响因子：
2.1
通讯作者：
Loffet, A
中科院分区：
文献类型：
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作者：
Loffet, A
第一个合成肽是在一个世纪前由埃米尔·菲舍尔（Emil Fischer）制备的，但合成肽的医疗用途是在第二次世界大战后才开始的，当时美国的杜·维格诺德（du Vigneaud）集团和瑞士的罗伯特·施维泽（Robert Schwyzer） （Ciba）和休格宁（Sandoz）工业集团可以制备纯肽。这是催产素和抗利尿激素（带有一个二硫桥的环状非肽）和血管紧张素的时代。肽的合成是一项漫长而艰巨的任务，用常规方法合成一个肽需要1-2年的时间。1963年，天才布鲁斯·梅里菲尔德（Bruce Merrifield）使用他命名为固相肽合成（Solid Phase Peptide Synthesis， SPPS）的方法加速并自动化了这一漫长的过程。由于新的纯化方法（高效液相色谱法）的发展，使一些难以置信的混合物得以纯化，这种方法的接受速度相当快。从20世纪60年代到本世纪末，多肽常被认为是未来的药物。它们的主要缺点是生物利用度低。此外，一些在多肽项目上投入巨资的大型制药公司不得不在后期临床阶段放弃其中一些项目。这促使他们发展了这个概念
The first synthetic peptide was prepared by Emil Fischer a century ago, but the medicinal use of synthetic peptides started after the Second World War, and only when peptides could be prepared pure by du Vigneaud’s group in the USA, and by the Swiss industrial groups of Robert Schwyzer (Ciba) and Huguenin (Sandoz). This was the time of oxytocin and vasopressin, cyclic nonapeptides with one disulphide bridge, and of the angiotensins. The synthesis of peptides was a long and difficult task, a single peptide taking 1–2 years to produce by conventional methods. It was the genius of Bruce Merrifield, in 1963, who hastened and automated this long process using the method he named Solid Phase Peptide Synthesis (SPPS). The acceptance of the method was rather fast, helped by the development of new purification methods (HPLC) which allowed purification of some incredible mixtures.From the 1960s to the end of the Millennium, peptides were often considered as the drugs of the future. Their main drawback was their low bioavailability. Further, some major pharmaceutical companies, which had invested heavily in peptide projects, had to drop some of these in the late clinical phase. This led them to develop the concept