Work

Rationalizing the structural basis of organic-platinum hybrid complexes binding towards quadruplex-duplex hybrids through all-atom simulations

Year: 2025

Type: article

Abstract: Guanine-rich sequences containing complementary base pairs can fold into non-canonical quadruplex-duplex hybrid (QDH) conformations. These structures possess unique structural features, leading to the presence of a peculiar binding pocket that can be distinguished from a canonical double helix or a G-quadruplex (G4) structure. Recently, two organic-metal hybrid platinum complexes, able to selectively and strongly recognize a particular type of QDH with a lateral duplex stem-loop, were reported in the literature. However, solution structures are not available for all the investigated compounds, leaving unanswered questions on the structural traits underlying the different binding affinity of these complexes. In this work, we address this gap using all-atom simulations to unravel the key features driving the high selectivity of these organic‑platinum hybrid complexes at an atomistic level. In particular, their binding affinity depends on a delicate balance between the extended π-π stacking interactions performed in the G4-duplex binding pocket and the capacity to form stable hydrogen bonds with the surrounding nucleobases. Thus, our findings provide essential insights to guide the rational design of novel compounds that selectively target QDH structures.

Source: Journal of Inorganic Biochemistry

DOI: 10.1016/j.jinorgbio.2025.112904

Authors: Salvatore Muscarella, Irene Treccarichi, Luisa D'Anna, Angelo Spinello

Institution: University of Palermo

Language: English

Topic: DNA and Nucleic Acid Chemistry

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,220

Funder: European Commission