To gain insight into the fundamental factors that affect the structure, stability and ligand binding properties of the intramolecular DNA quadruplex formed from the human telomere sequence (TTAGGG)4, a library of DNA sequences, (XXXGGG)y where X = T or A and y = 1, 2, 4 or 8, was generated and characterized by circular dichroism (CD). The wild type sequence folds into a distinct conformation with particular strand and loop orientations. The GGG bases form a G-tetrad while the second, third and fourth TTA segments are found in the loops joining the tetrads. Our initial findings from CD analyses indicate that the conformations of these oligomers are dependent upon sequence context (identity of X), number of repeats (value of y) and cation (Na+ or K+) present. © 2011 American Chemical Society.