HIV-1 integrase inhibitor T30177 forms a stacked dimeric G-quadruplex structure containing bulges

Abstract

T30177 is a G-rich oligonucleotide with the sequence (GTGGTGGGTGGGTGGGT) which inhibits the HIV-1 integrase activity at nanomolar concentrations. Here we show that this DNA sequence forms in K+ solution a dimeric G-quadruplex structure comprising a total of six G-tetrad layers through the stacking of two propeller-type parallel-stranded G-quadruplex subunits at their 5′-end. All twelve guanines in the sequence participate in the G-tetrad formation, despite the interruption in the first G-tract by a thymine, which forms a bulge between two adjacent G-tetrads. In this work, we also propose a simple analytical approach to stoichiometry determination using concentration-dependent melting curves.