核酶
化学
组合化学
翻译(生物学)
肽
环肽
药物发现
计算生物学
分子内力
小分子
转移RNA
纳米技术
立体化学
生物化学
生物
核糖核酸
信使核糖核酸
材料科学
基因
作者
Christos Tsiamantas,Manuel E. Otero-Ramirez,Hiroaki Suga
出处
期刊:Methods in molecular biology
日期:2019-01-01
卷期号:: 299-315
被引量:17
标识
DOI:10.1007/978-1-4939-9504-2_14
摘要
Flexizymes, highly flexible tRNA aminoacylation ribozymes, have enabled charging of virtually any amino acid (including non-proteogenic ones) onto tRNA molecules. Coupling to a custom-made in vitro translation system, namely the flexible in vitro translation (FIT) system, has unveiled the remarkable tolerance of the ribosome toward molecules, remote from what nature has selected to carry out its elaborate functions. Among the very diverse molecules and chemistries that have been ribosomally incorporated, a plethora of entities capable of mediating intramolecular cyclization have revolutionized the design and discovery of macrocyclic peptides. These macrocyclization reactions (which can be spontaneous, chemical, or enzymatic) have all served as tools for the discovery of peptides with natural-like structures and properties. Coupling of the FIT system and mRNA display techniques, known as the random non-standard peptide integrated discovery (RaPID) system, has in turn allowed for the simultaneous screening of trillions of macrocyclic peptides against challenging biological targets. The macrocyclization methodologies are chosen depending on the structural and functional characteristics of the desired molecule. Thus, they can emanate from the peptide’s N-terminus or its side chains, attributing flexibility or rigidity, or even result in the installation of fluorescent probes.
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