Linear and Branched Pyridyl-Oxazole Oligomers: Synthesis and Circular Dichroism Detectable Effect on c-Myc G-Quadruplex Helicity

Abstract

Five unprecedented pyridyl-oxazole oligomers exhibiting either linear or branched connectivity of their subunits were developed as a family of potential G-quadruplex-interacting ligands. Our synthesis employed variations of a key Pd/Cu-mediated C-C cross-coupling/C-H activation reaction to gain access to the oligomer products from a small set of substituted pyridine building blocks. The effect of the compounds on the conformation of a c-myc oncogene promoter G-quadruplex was investigated by circular dichroism under various conditions. Some or all of the compounds induced detectable helicity enhancement in low-cation and Na+-rich Tris-HCl (pH 7.4) buffers, respectively, in which the helix was only partially prefolded.