G-quadruplex conformational selectivity by Zn(II) porphyrins bearing sperminate substituents

G-quadruplex (GQ) DNA structures potentially exist at the telomeres of eukaryotic chromosomes, as their repetitive G-rich sequences (e.g., TTAGGG in mammals) are known to adopt such non-canonical DNA structures in vitro. In the crystalline state, human telomeric DNA preferentially folds into an all-parallel conformation with three TTA propeller loops.[1] Under dilute solution conditions in Na+ buffer, telomeric DNA folds into an antiparallel conformation,[2] and in K+ buffer it adopts three mixed-polarity conformations depending on the exact sequence.[1] It has been shown that small organic molecules can inhibit telomerase by inducing and stabilizing G-quadruplex structures of human telomeric ssDNA.[3] In most cases, typical G-quadruplex stabilizing telomerase inhibitors are characterized by the presence of an aromatic planar area and from two up to four positively charged side chains.[4] Interactions of natural products with genetic material, have been at the center of large number of studies for several years. Porphyrinoids are ideal compounds to be incorporated into DNA due to peculiar characteristics. It has been showed that cationic porphyrins have been utilized as reporters of different sequences and conformations of single and duplex DNA. [5-6] GQ structures can be stabilized by small molecule ligands including porphyrins.[7] Ligands that can selectively stabilize GQs but not double-stranded DNA (dsDNA) may have potential applications as pharmaceuticals for cancer therapy. We explore by CD, UV, FRET and melting experiments the different effects showed by new cationic porphyrin bearing sperminate substituents in the presence of different conformations of GQ obtained by models of G-rich sequences (Tel22 and TG3AG).