Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
ACS Comb Sci. 2020 Dec 14;22(12):712-733. doi: 10.1021/acscombsci.0c00179. Epub 2020 Nov 9.
The power of ribosomes has increasingly been harnessed for the synthesis and selection of molecular libraries. Technologies, such as phage display, yeast display, and mRNA display, effectively couple genotype to phenotype for the molecular evolution of high affinity epitopes for many therapeutic targets. Genetic code expansion is central to the success of these technologies, allowing researchers to surpass the intrinsic capabilities of the ribosome and access new, genetically encoded materials for these selections. Here, we review techniques for the chemical expansion of genetically encoded libraries, their abilities and limits, and opportunities for further development. Importantly, we also discuss methods and metrics used to assess the efficiency of modification and library diversity with these new techniques.
核糖体的功能已逐渐被用于分子文库的合成和筛选。噬菌体展示、酵母展示和 mRNA 展示等技术有效地将基因型与表型偶联，用于许多治疗靶点的高亲和力表位的分子进化。遗传密码扩展是这些技术成功的核心，使研究人员能够超越核糖体的固有能力，并为这些选择获得新的遗传编码材料。在这里，我们回顾了用于化学扩展遗传编码文库的技术，及其能力和限制，以及进一步发展的机会。重要的是，我们还讨论了使用这些新技术评估修饰效率和文库多样性的方法和指标。
