5′-Phosphorylation Strengthens Sticky-End Cohesions

Sticky-end cohesion plays a critical role in molecular biology and nucleic acid nanotechnology. Although free energy calculations and molecular mechanics can predict these interactions, chemical modification would compromise such predictions. Herein, we have used rationally designed 3D DNA crystals as a tool to experimentally investigate the modulation of 5′-phosphorylation on sticky-end cohesions. We have found that 5′-phosphorylation strengthens the sticky-end cohesion: in a DNA crystal self-assembled exclusively via sticky-end cohesions, 5′-phosphorylation not only promotes the crystallization process, in general, but also accelerates the crystal growth along designed directions. Such a finding allows the fine-tuning of DNA crystallization kinetics and the control of DNA crystal morphology. It also suggests a potential difference in self-assembly kinetics between natural DNA (with 5′-phosphorylation) and synthetic DNA (without 5′-phosphorylation).