A novel trend in G-quadruplexligand design is to build a binder that is able to not only discriminate G-quadruplex from duplex-DNA, but also among various G-quadruplex structures. Methylazacalix[6]pyridine (MACP6), a new type of azacalixarene with flexible conformation, exhibits induced circular dichroism signals when interacted with most of G-quadruplexes. The intensities of the induced signals are strongly dependent on the topology of G-quadruplexes. Further evidence has shown that these signals can be ascribed to the preferred binding of MACP6 to the loops of G-quadruplexes, which rely on the nature of nucleotides in the loops.