Insights into the G‐quadruplex DNA interaction landscape: Comparative analysis of anionic Zn(II) and Co(II) phthalocyanine‐tetrasulfonate complexes

Abstract

G‐quadruplexes play a pivotal role in regulating various cellular processes, including gene expression and replication, making them essential structures in understanding, and manipulating cellular functions. The development of G‐quadruplex ligands holds significant promise in therapeutic and research applications, offering targeted tools to modulate G‐quadruplex structures and potentially influence critical biological pathways. An exciting frontier in G‐quadruplex research lies in the exploration of anionic ligands, and their profound impact on stabilizing and modulating G‐quadruplex DNA. In this study, the interaction of two anionic phthalocyanine compounds (Zinc (II) phthalocyanine 3,4′,4″,4‴‐tetrasulfonic acid, tetrasodium salt, ZnAPC; cobalt (II) phthalocyanine 3,4′,4″,4‴‐tetrasulfonic acid, tetrasodium salt, CoAPC) and three separate G‐quadruplex‐forming DNA sequences was investigated. Interactions were carried out by DNA polymerase stop studies along with spectroscopic studies. According to the results of experimental data, it was determined that ZnAPC actively interacts with the G‐quadruplex DNA structures. On the other hand, it was thought that the interaction with CoAPC was less and even occurred in simple electrostatic interactions. KD constants and Bmax constants for the interaction with ZnAPC were calculated. The KD constants for ZnAPC were found to be (1.16 ± 0.07) × 10−5, (9.75 ± .24) × 10−6 and (1.00 ± 0.36) × 10−4 M for AS1411, Vegf, and Tel21, respectively. Accordingly, it was concluded that ZnAPC interacts with G‐quadruplex DNA ligands effectively.