History
As early as 1964, Irving Goldberg and co-workers introduced the idea that small molecules, such as actinomycin D, that interact with DNA could have sequence selectivity.
In 1968, Donald Crothers and co-workers provided biophysical evidence for the intercalation of actinomycin D into DNA.
X-ray crystallographic studies by Hank Sobell and colleagues at the University of Rochester provided molecular insight into the basis for this sequence selectivity. These studies, although profound in themselves, went largely unnoticed by the chemical community until the first X-ray structures of restriction enzymes bound to DNA refocused interest on small molecules that could recognize DNA.
The discovery of minor-groove-recognition molecules, such as distamycin and netropsin, paved the way for considering the design and synthesis of DNA code-reading molecules that might ultimately target a unique sequence: a 13-16 base-pair (bp) sequence is required to select a unique sequence in a human genome of 2.3 billions of bp.
Major-groove-recognition molecules followed and the race was on to direct genetic events by targeting duplex DNA with either minor- or major-groove-recognition molecules.