Membrane‐Penetrating Molecular Device Based on a Triplex Containing Acyclic L‐Threoninol Nucleic Acid Functionalized with Cholesterol

Membrane-penetrating molecular devices are valuable biological tools. Herein, we describe membrane-targeting molecular devices based on the triplexes of poly T acyclic L-threoninol nucleic acid (L-aTNA) tethered site-specifically to cholesterol and poly A DNA. The L-aTNA was linked to cholesterol in two different orientations. The membrane-binding properties differed depending on the orientation at the cholesterol linkage. One triplex adhered to giant unilamellar vesicles and the other penetrated these vesicles. When the membrane-penetrating triplex was formed with a photoresponsive DNA, photoresponsive signal transduction into giant unilamellar vesicles was enabled. These membrane-targeting molecular devices have potential as biosensors, artificial organs, and molecular robots and in chemical artificial intelligence. Moreover, this strategy for post-modification of the propargyl-L-aTNA unit will enable further functionalization of L-aTNA and other acyclic XNAs.