A versatile water soluble ball-type phthalocyanine as potential antiproliferative drug: the interaction with G-quadruplex formed from Tel 21 and cMYC

Abstract

G-quadruplexes are biologically important DNA conformations exist generally in guanine rich segments of DNA, such as telomere and proto-oncogene.
The formation of these secondary structures is thought to inhibit the expression of certain genes, such as the inhibition of telomerase. The inhibition of telomerase and suppression of a specific gene expression are important approaches for interruption of cancer cell's proliferation. In the present study, the effect of a versatile water soluble ball-type phthalocyanine on G-quadruplex formation and stabilization was investigated to demonstrate its potential usage in cancer chemotherapy. Two important guanine rich oligomers, cMYC and Tel 21 were used as G-quadruplex former sequence. To the best of our knowledge, this is the first study about the interaction of a ball-type phthalocyanine with G-quadruplex structures.  The interactions of the compound with G-quadruplex molecules were monitored spectrophotometrically. The structural differentiations of G-quadruplex after binding were investigated with circular dichroism spectrophotometry. The replacement ability of the molecule with a known DNA binding molecule, ethidium bromide, was clarified fluorometrically. The Stern-Volmer studies were conducted for determination of the quenching mechanism. The strong interaction of the molecules (ball-type phthalocyanine with oligomer) showed us the potential usage of these drug conjugates for targeted photodynamic therapy in the future. 

Keywords

• G-quadruplex,CD spectroscopic titration,telomere,oncogene

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