Synthetic studies towards molecular recognition of guanosine quadruplexes

The telomere is a guanine-rich region of DNA located at its termini. Each time a DNA molecule is replicated, the telomere gets shortened. Cell death occurs after a telomere has been shortened to a critical length. The telomere may, however, be re-lengthened by the action of the enzyme telomerase. It has been found that in many cases of cancer, the level of telomerase in the cells is extremely high when compared to normal cells. The telomeric region may be linear, or may adopt higher-order structures such as the G-quadruplex. When the telomere is in G-quadruplex form, telomerase is unable to bind to the region and re-lengthen it. By designing molecules that can recognize the G-quadruplex and bind to them, therefore stabilizing them, it is theorized that telomerase inhibition may occur.

Through the use of computational methods, an oligomer has been designed to recognize the minor groove of a G-quadruplex. The oligomer has a recognition unit of an aminopyridine group and a peptide nucleic acid (PNA) backbone. The synthetic route to the monomers required for solid-phase synthesis of this oligomer is described in detail.