A functional group-guided approach to aptamers for small molecules

• 成果类型: Article
• 署名作者: Yang, Kyungae; Mitchell, Noelle M.; Banerjee, Saswata; Cheng, Zhenzhuang; Taylor, Steven; Kostic, Aleksandra M.; Wong, Isabel; Sajjath, Sairaj; Zhang, Yameng; Stevens, Jacob; Mohan, Sumit; Landry, Donald W.; Worgall, Tilla S.; Andrews, Anne M.; Stojanovic, Milan N.
• 署名单位: NewYork-Presbyterian Hospital; Columbia University; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; NewYork-Presbyterian Hospital; Columbia University; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; NewYork-Presbyterian Hospital; Columbia University; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; Howard Hughes Medical Institute; Rockefeller University; California Institute of Technology
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13724
• DOI: 10.1126/science.abn9859
• 发表日期: 2023-06-02
• 页码: 942-948
• 关键词: in-vitro selection; rna ligands; EVOLUTION; binding; identification; voriconazole; reactivity

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.