Post–Column Guanosine Addition as a Screening Tool in the Search for Effective G–Quadruplex Binders—A Case Study of Achyrocline satureioides Phenolic Compounds

TL;DR

This study explores how certain plant compounds bind to G-quadruplex structures, which may help in developing anticancer drugs.

Contribution

A new screening method using post-column guanosine addition is proposed to evaluate G-quadruplex binding potential of polyphenols.

Findings

The tested compounds from Achyrocline satureioides form more stable adducts with deoxyguanosine and guanosine than isoquercitrin and rutin.

Molecular docking suggests multiple interactions are crucial for the stability of polyphenol-G-quadruplex adducts.

Abstract

Polyphenols make a numerous and diverse group of plant secondary metabolites exhibiting remarkable anticancer activities, often attributed to their G-quadruplex binding properties. Therefore, there is a need to develop a high–throughput screening assay which would permit the evaluation of polyphenols’ binding properties toward G-quadruplex. As deoxyguanosine and guanosine are essential and key building blocks of G-quadruplexes, the stabilities of their adducts with polyphenols may reflect the stabilities of polyphenols–G-quadruplex adducts. In this study, deoxyguanosine/guanosine post-column addition experiments have been performed during HPLC-MS analysis of Achyrocline satureioides extract. The stabilities of the deoxyguanosine/guanosine adducts with 3-O-methylquercetin-7-O-glucoside, 4′-hydroxydehydrokawain-4′-O-glucoside, and 3,5-di-O-caffeoylquinic acid—compounds identified in the Achyrocline satureioides extract—have been tested by using collision-induced dissociation ‘in-source’. The obtained results show that the identified compounds form more stable adducts with deoxyguanosine and guanosine than the standards used for comparison, namely isoquercitrin and rutin. The performed molecular docking provided some insight into the structure of the adducts and revealed that multiple interactions are of key importance for their stabilities.

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