Kinetics of tetramolecular quadruplexes

The melting of tetramolecular DNA or RNA quadru-plexes is kinetically irreversible. However, rather than being a hindrance, this kinetic inertia allows us to study association and dissociation processes independently. From a kinetic point of view, the association reaction is fourth order in monomer and the dissociation first order in quadruplex. The association rate constant kon, expressed in M 3s1 decreases with increasing temperature, reflecting a negative activation energy (Eon) for the sequences presented here. Association is favored by an increase in monocation concentration. The first-order dissoci-ation process is temperature dependent, with a very positive activation energy Eoff, but nearly ionic strength independent. General rules may be drawn up for various DNA and RNA sequence motifs, invol-ving 3–6 consecutive guanines and 0–5 protruding bases. RNA quadruplexes are more stable than their DNA counterparts as a result of both faster associ-ation and slower dissociation. In most cases, no dis-sociation is found for G-tracts of 5 guanines or more in sodium, 4 guanines or more in potassium. The data collected here allow us to predict the amount of time required for 50 % (or 90%) quadruplex formation as a function of strand sequence and concentration, tem-perature and ionic strength