Discovering peptide ligands using epitope libraries.
Discovering peptide ligands using epitope libraries.
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使用表位库发现肽配体。
DOI：
10.1016/0968-0004(92)90401-t
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发表时间：
1992
影响因子：
13.8
通讯作者：
Scott,JK
中科院分区：
文献类型：
--
作者：
Scott,JK
表位图书馆的基础来自两个平行的发展。Mario Geysen开创了这样的概念：(1)含有关键结合残基的短肽(模拟表位)可以在化学上模拟蛋白质(表位)上折叠的抗原决定簇；(2)在许多情况下，表位的几个关键残基与其结合分子或连接体*之间形成的非共价键可能对总结合能有很大贡献。几乎在同一时间，Stephen Parmley和George Smith开发了一种可以在其表面展示外源表位的噬菌体表达载体2。该载体可以用来构建大量的噬菌体集合，几乎可以包括一个短(如六个氨基酸)肽的所有可能的序列。他们还开发了生物扫描，这是一种使用特定抗体2亲和纯化展示外源表位的噬菌体的方法。受Geysen的工作启发，Smith、McCutchan和De la Cruz假设，应该可以使用最近开发的表达载体和生物扫描技术从给定长度的所有可能序列中识别模拟表位。这导致了通过生物扫描表位文库来识别抗体的多肽配体的想法，然后这些表位文库可以用于疫苗设计、表位绘制、基因鉴定和许多其他应用2。另一些人建议推广使用表位文库来寻找其他受体、酶和其他配体的模拟多肽配体，这在药物发现方面将具有巨大的潜力。
THE FOUNDATION FOR epitope libraries came from two parallel developments. Mario Geysen pioneered the concepts that (1) short peptides bearing critical binding residues (mimotopes) can chemically mimic the folded antigenic determinants on proteins (epitopes), and,(2) in many cases, the non-covalent bonds formed between a few critical residues from an epitope and its binding molecule or ligate* may make a major contribution to the total energy of binding. At about the same time, Stephen Parmley and George Smith developed a bacteriophage expression vector that could display foreign epitopes on its surface 2. This vector could be used to construct large collections of bacteriophage which could include virtually all possible sequences of a short (eg six-amino-acid) peptide. They also developed biopanning, a method for affinity-purifying phage displaying foreign epitopes using a specific antibody 2.Inspired by Geysen's work, Smith, McCutchan and de la Cruz postulated that it should be possible to use the recently developed expression-vector and biopanning technique to identify mimotopes from all possible sequences of a given length. This led to the idea of identifying peptide ligands for antibodies by biopanning epitope libraries, which could then be used in vaccine design, epitope mapping, the identification of genes and many other applications 2. Others suggested generalizing the use of epitope libraries to finding mimetic peptide ligands for other receptors, enzymes and other ligates, which would have tremendous potential in terms of drug discovery.