Acid-facilitated Supramolecular Assembly of G-quadruplexes in d(CGG)β4

Abstract Molar [K] induces aggregate formation in d(CGG), as evidenced by absorbance, circular dichroic (CD), and gel measurements. The kinetics of this transformation are extremely slow at pH 8 but are found to be greatly facilitated in acidic conditions. Kinetic profiles via absorbance or CD monitoring at single wavelength resemble those of autocatalytic reacting systems with characteristic induction periods. More than 0.8 M KCl is needed to observe the onset of aggregation at 20°C and pH 5.4 within the time span of 1 day. Time-dependent CD spectral characteristics indicate the formation of parallel G-tetraplexes prior to the onset of aggregation. Despite the evidence of K-induced parallel G-quadruplex and higher molecular weight complex formation, both d(TGG) and d(CGG)T fail to exhibit the observed phenomenon, thus strongly implicating the crucial roles played by the terminal G and base protonation of cytosines. A plausible mechanism for the formation of a novel self-assembled structure is speculated. Aided by the C•C base pair formation, parallel quadruplexes are initially formed and subsequently converted to quadruplexes with contiguous G-tetrads and looped-out cytosines due to high [K]. These quadruplexes then vertically stack as well as horizontally expand via inter-quadruplex C•C base pairing to result in dendrimer-type self-assembled super structures.