Scholarlink

<p>A challenge in chemical biology is to study structure-activity relationships (SAR) in vivo in cells. Multiplexed activity profiling (MAP), developed for natural product discovery, is well-suited to address this challenge as it is high throughput, singlecell, and measures multiple hallmark cellular functions. Applying MAP while systematically varying molecular structure (SAR-MAP) could reveal previously unappreciated activity within chemical families and prioritize candidate molecules for further characterization. Here we use SAR-MAP to identify structural features responsible for specific bioactivities of the natural product family, rocaglates. MV411 leukemia cells and healthy human leukocytes are selected for proof-of-concept screening. Testing 600 representative molecules using MAP classifies roughly half of tested rocaglates (9 of 19) as bioactive. SAR-MAP elucidates a methoxy substituent on select rocaglate pyrimidinones as responsible for a desirable anti-leukemia activity. Thus, SAR-MAP can be immediately applied to identify structural variations driving natural product activity in cell lines and primary human cells.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Connecting chemical structure to single cell signaling profiles

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月31日

查看全文
  • Hannah L. Thirman,
  • Madeline J. Grider-Hayes,
  • Laura C. Geben,
  • Rebecca A. Ihrie,
  • Lauren E. Brown,
  • John A. Porco Jr,
  • Jonathan M. Irish

摘要

A challenge in chemical biology is to study structure-activity relationships (SAR) in vivo in cells. Multiplexed activity profiling (MAP), developed for natural product discovery, is well-suited to address this challenge as it is high throughput, singlecell, and measures multiple hallmark cellular functions. Applying MAP while systematically varying molecular structure (SAR-MAP) could reveal previously unappreciated activity within chemical families and prioritize candidate molecules for further characterization. Here we use SAR-MAP to identify structural features responsible for specific bioactivities of the natural product family, rocaglates. MV411 leukemia cells and healthy human leukocytes are selected for proof-of-concept screening. Testing 600 representative molecules using MAP classifies roughly half of tested rocaglates (9 of 19) as bioactive. SAR-MAP elucidates a methoxy substituent on select rocaglate pyrimidinones as responsible for a desirable anti-leukemia activity. Thus, SAR-MAP can be immediately applied to identify structural variations driving natural product activity in cell lines and primary human cells.