Third-strand stabilizing effects of the RNA poly(U)·poly(A)*poly(U) triplex by a ruthenium(II) polypyridine complex and its hexaarginine peptide conjugate.

In this work, a Ru(II) complex [Ru(bpy)2(pip-CO2H)]2+ (Ru1) and its hexaarginine peptide conjugate [Ru(bpy)2(pic-Arg6)]8+ (Ru2) have been synthesized and characterized. The binding of Ru1 and Ru2 with poly(U)•poly(A)*poly(U) triplex has been studied. Results suggest that Ru1 binds in the surface of the minor groove while Ru2 binds to the minor groove of the triplex. Consequently, the triplex stabilization is barely affected by Ru1, while with Ru2 the triplex stabilizing effect is so strong that that dissociation of the triplex shows an overlapping of both melting processes with the melting temperature increased to a maximum of 56.1 °C at the CRu2/CUAU ratio of 0.05, where ΔTm1 and ΔTm2 are 19.6 and 10.1 °C, respectively. Furthermore, the effect of Ru2 stabilizing the third strand at such a low binding ratio of 0.05 is more marked than what obsereved for flavone luteolin and [Ru(bpy)2(mdpz)]2+, which are so far the strongest triplex stabilizers in the reported organic small molecules and metal complexes, respectively. Considering the structure natures of Ru2, conceivably except for electrostatic interaction, the forces stabilizing the triplex should also involve hydrophobic interaction and hydrogen bingding. To our knowledge, this work represents a first example of improving the triplex stabilization by a metallopeptide.