Solution Structure of a Prion Protein Aptamer Analogue

It has previously been shown that r(GGA)4 folds into a G-quadruplex structure, which binds to the normal cellular form of the prion protein (PrPC) with high affinity. The current study utilizes CD and NMR spectroscopy to show that a dimeric parallel G-quadruplex structure is formed by r(GGA)2 in a KCl solution. Each r[(GGA)2]2 G-quadruplex unit exhibits two G-quartets, one of which is hydro- gen bonded to two additional adenines forming a hexade. Through stacking of hexade planes, two G-quadruplex units interact with each other and form a symmetric dimer, r[(GGA)2]4. The topolo¬gy of r[(GGA)2]4 is in agreement with the fold of r[(GGA)4]2, however, subtle differences are found in the region responsible for PrPC binding