Quadruplex Structure of Polyriboinosinic Acid:  Dependence on Alkali Metal Ion Concentration, pH and Temperature

Abstract

The vibrational infrared (IR) absorption and vibrational circular dichroism (VCD) spectral changes of polyinosinic acid (polyI) as a function of alkali metal ion concentration, temperature and pH have been investigated to establish how changes in spectral features relate to the structural modifications of polyI. A single positive VCD couplet associated with the carbonyl absorption band is considered to be the signature of quadruplex structure for polyI. The disruption of the quadruplex structure with temperature increase or pH increase at low alkali metal ion concentration is evidenced by the disappearance of this positive VCD couplet. The absence of any VCD signal upon quadruplex disruption indicates that the newly formed structure lacks helical chirality and is likely to be disordered. In the presence of 1 M NaCl or 0.1 M NaCl, the heat-induced quadruplex disruption is completely reversible. A mildly alkaline environment, in the presence of 0.1 M NaCl, is not sufficient to support the quadruplex structure of polyI. Trehalose-assisted polyI film at room temperature exhibits the same quadruplex spectral signature as that seen for solution at room temperature, but the quadruplex spectral signature in the film state remains at higher temperature, unlike in solution. This indicates that the quadruplex structure of polyI in the film state resists heat-induced disruptions.

Polyphosphate and RNA Differentially Modulate the Contact Pathway of Blood Clotting

“…3 On the other hand, previous work by Gansler et al (37) demonstrated the importance of secondary structure on the procoagulant ability of nucleic acids, finding that hairpin-forming RNA oligomers are not only more resistant to degradation but are also more procoagulant, and in particular, structure-forming RNA aptamers were shown to mediate PPK autoactivation. PolyG and polyI are known to form stable, non-canonical base-pairing structures such as G-quadruplexes (38,39). We previously reported that polyG RNA has substantial procoagulant activity (40,41).…”

Calculation of Hydrodynamic Properties for G-Quadruplex Nucleic Acid Structures from in silico Bead Models

“…The other structure, 2KKA, was excluded because the reported structure contained a non-canonical inosine substituted for a guanine. Inosine disrupts G-quadruplex formation [70] and is used reduce the number of possible folding topologies for a polymorphic G-quadruplex sequence. Instead of using this structure to build our global fit model, we selected it to study how base substitution affects the structure in solution.…”

Bioinspired interactions studied by vibrational circular dichroism

“…40,42 Infrared absorption and VCD changes correlate with structural changes of both polymers. The computations reported here were performed in a rough manner and provide preliminary results.…”

“…VCD was also used for the investigation of quadruplex structures formed in the homopolynucleic acids polyriboguanylic (polyG) and polyriboinosinic acid (polyI). 40,42 Infrared absorption and VCD changes correlate with structural changes of both polymers. The computations reported here were performed in a rough manner and provide preliminary results.…”