Clackson T, Wells J A
Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.
Trends Biotechnol. 1994 May;12(5):173-84. doi: 10.1016/0167-7799(94)90079-5.
In vitro selection from molecular libraries has rapidly come of age as a protein-engineering tool. Dramatic increases in protein affinity can be engineered using phage-display libraries, and specific antibodies can be selected directly from a single 'naïve' library of their genes. Repertoires of small molecules are a potentially valuable resource for drug discovery. Libraries of linear peptides provide ligands for proteins that recognize continuous epitopes, and low-affinity mimics of some small molecules, but generally do not contain mimics of large molecular interfaces. Switching to constrained peptide formats, and deploying more diverse, non-peptide chemical libraries, may bring greater success.
作为一种蛋白质工程工具，从分子文库中进行体外筛选迅速走向成熟。利用噬菌体展示文库可以设计出蛋白质亲和力的显著提高，并且可以直接从单个“原始”基因文库中筛选出特异性抗体。小分子文库是药物发现的潜在宝贵资源。线性肽文库为识别连续表位的蛋白质提供配体，以及一些小分子的低亲和力模拟物，但通常不包含大分子界面的模拟物。转向受限肽形式，并部署更多样化的非肽化学文库，可能会带来更大的成功。
