Naphthalenediimide and its Congeners: From Molecules to Materials
Chapter 2: NDI as a DNA Intercalator
Published:15 Mar 2017
Naphthalene diimide (NDI) has been widely studied as a DNA threading intercalator. While an intercalator binds DNA by insertion in between base pairs, a threading intercalator also binds with substituents residing simultaneously in the DNA major and minor grooves. The ease with which NDI can be modified through its two imide functionalities has allowed it to be used as a scaffold for threading polyintercalation, where multiple NDI intercalators are connected through linkers that are designed to alternate binding between the major and minor grooves, analogous to the way a snake might climb a ladder. The Iverson lab in particular has been exploring NDI threading polyintercalation based on tethering NDI units in a head-to-tail manner with peptide linkers. Peptide linkers derived from library screens have led to threading NDI polyintercalators that display exquisite sequence specificity. Further, the modular nature of the threading polyintercalator design enables binding to relatively long DNA sequences. Recognition of a 22 base-pair sequence and a dissociation half-life of around 60 days have been achieved with different threading NDI polyintercalators, representing the longest recognition sequence and slowest dissociation rate yet reported for synthetic, non-nucleic acid-based molecules.