While the majority of small molecule chemical probes and drugs to date modulate the action of proteins, the Hargrove Lab is searching for small molecules that selectively engage binding pockets of RNA. In their most recent work, the group discovered the first ligands for the triple helix structure of an oncogenic long non-coding RNA MALAT1. The synthesis, evaluation and computational analysis of these novel small molecules revealed trends between small molecule shapes and their binding behavior. Together, these unprecedented insights provide strategies for tuning molecules towards selective binding to this important therapeutic target, and are expected to encourage future efforts in small molecule-based targeting of lncRNAs with emerging roles in disease biology. Read more about this exciting work in Angewandte Chemie International Edition’s Early View manuscripts here.