适体
计算生物学
功能多样性
合作性
功能群
寡核苷酸
位阻效应
生物
化学
立体化学
生物化学
遗传学
DNA
生态学
有机化学
聚合物
作者
Kiyull Yang,N. J. Mitchell,Saswata Banerjee,Zhenzhuang Cheng,Steven Taylor,Aleksandra M. Kostic,Isabel Wong,Sairaj Munavar Sajjath,Yameng Zhang,Jacob S. Stevens,Sumit Mohan,Donald W. Landry,Tilla S. Worgall,Anne M. Andrews,Milan N. Stojanović
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2023-06-02
卷期号:380 (6648): 942-948
被引量:23
标识
DOI:10.1126/science.abn9859
摘要
Aptameric receptors are important biosensor components, yet our ability to identify them depends on the target structures. We analyzed the contributions of individual functional groups on small molecules to binding within 27 target-aptamer pairs, identifying potential hindrances to receptor isolation—for example, negative cooperativity between sterically hindered functional groups. To increase the probability of aptamer isolation for important targets, such as leucine and voriconazole, for which multiple previous selection attempts failed, we designed tailored strategies focused on overcoming individual structural barriers to successful selections. This approach enables us to move beyond standardized protocols into functional group–guided searches, relying on sequences common to receptors for targets and their analogs to serve as anchors in regions of vast oligonucleotide spaces wherein useful reagents are likely to be found.
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