Hoogsteen

Hoogsteen refers to a noncanonical base-pairing geometry observed in nucleic acids, named after the Dutch-born chemist J. Hoogsteen who first described it in 1963. Unlike the standard Watson-Crick arrangement, in a Hoogsteen base pair the purine base (adenine or guanine) adopts a syn conformation so that hydrogen bonding uses the purine’s Hoogsteen edge rather than its Watson-Crick edge. The result is a distinct hydrogen-bond pattern and a geometry that is typically shorter and wider than a Watson-Crick pair. In A–T Hoogsteen pairs, and G–C Hoogsteen pairs, the partner base complements the Hoogsteen edge via alternative donors and acceptors.

Hoogsteen base pairing can occur transiently in B-form DNA and is more common under certain conditions, such as chemical modification, acidic pH, or in the presence of ligands or proteins that destabilize the canonical duplex. It is also a central feature of in vitro DNA structures such as triple helices (H-DNA) and certain DNA crystals, where a third strand binds via Hoogsteen contacts in the major groove.

In modern structural biology the Hoogsteen geometry is recognized as a legitimate alternative to Watson-Crick in specific contexts. The concept also includes reverse Hoogsteen base pairs, where the hydrogen-bonding pattern is inverted relative to the classic Hoogsteen arrangement. Understanding Hoogsteen pairing helps explain local duplex flexibility, DNA recognition, and the conformational repertoire of nucleic acids.