4.8 Article

An amber obligate active site-directed ligand evolution technique for phage display

期刊

NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -

出版社

NATURE RESEARCH
DOI: 10.1038/s41467-020-15057-7

关键词

-

资金

  1. National Institutes of Health [R01CA161158]
  2. Cancer Prevention and Research Institute of Texas [RP170797]
  3. Welch Foundation [A-1715]
  4. National Science Foundation [1566601, 1664866, 1900549]
  5. Laboratory for Molecular Simulation (LMS) at Texas AM University
  6. Direct For Mathematical & Physical Scien
  7. Division Of Chemistry [1664866, 1566601] Funding Source: National Science Foundation
  8. Division Of Chemistry
  9. Direct For Mathematical & Physical Scien [1900549] Funding Source: National Science Foundation

向作者/读者索取更多资源

Although noncanonical amino acids (ncAAs) were first incorporated into phage libraries through amber suppression nearly two decades ago, their application for use in drug discovery has been limited due to inherent library bias towards sense-containing phages. Here, we report a technique based on superinfection immunity of phages to enrich amber-containing clones, thus avoiding the observed bias that has hindered incorporation of ncAAs into phage libraries. We then take advantage of this technique for development of active site-directed ligand evolution of peptides, where the ncAA serves as an anchor to direct the binding of its peptides to the target's active site. To demonstrate this, phage-displayed peptide libraries are developed that contain a genetically encoded butyryl lysine and are subsequently used to select for ligands that bind SIRT2. These ligands are then modified to develop low nanomolar inhibitors of SIRT2.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据