Characterization of potassium binding with XXXX telomeres.

@entity1 @entity3529 @entity5
UNASSIGNED: @entity1 telomeres are G-rich tandem repeats that assume G-quadruplex structures at the ends of chromosomes. Stabilization of telomeric G-quadruplex represents a significant drug target for inhibiting the telomerase activity that is required in ~85% of @entity5 . Metal ions have been revealed as important stabilizers to DNA G-quadruplexes, but their binding process with @entity1 telomeric G-quadruplex remains unclear. In this report, we show that @entity3529 traverses into the G-tetrads center of two G-tetrad layers through the half-capped top pathway constructed by the two edge-wise loop bases. The binding is mediated by the electrostatic interactions between @entity3529 and the nearby bases of G-tetrads. However, direct traverse of @entity3529 into the interior of G-quadruplex is negatively regulated by the steric hindrance of water molecules. Once @entity3529 enters the G-quadruplex, stabilization of the in-plane or sandwiched conformation of the telomeric G-quadruplex- @entity3529 complex is maintained by surrounding water molecules. These findings provide insights into the atomic interactions between @entity3529 and telomere G-tetrads for targeted drug design. This article is protected by copyright. All rights reserved.
