Recognition of Nucleic Acid Junctions Using Triptycene-Based Molecules

The modulation of nucleic acids by small molecules is an essential process across the kingdoms of life. Targeting nucleic acids with small molecules represents a significant challenge at the forefront of chemical biology. Nucleic acid junctions are ubiquitous structural motifs in nature and in designed materials. Herein, we describe a new class of structure‐specific nucleic acid junction stabilizers based on a triptycene scaffold. Triptycenes provide significant stabilization of DNA and RNA three‐way junctions, providing a new scaffold for the development of nucleic acid junction binders with enhanced recognition properties. Additionally, we report cytotoxicity and cell uptake data in two human ovarian carcinoma cell lines. Structure and function: A new class of structure‐specific nucleic acid junction binders based on a triptycene scaffold provides significant stabilization of DNA and RNA three‐way junctions (3WJs). Initial biological studies with these junction binders show promising cytotoxicity in cisplatin‐resistant human ovarian carcinoma cell lines and positive cellular uptake.