A complementary chemical probe approach towards customized studies of G-quadruplex DNA structures in live cells

• DOI: 10.1039/d1sc05816a
• Publication Date: 2022-02-01T11:30:57Z
• Authors: Bagineni Prasad; Mara Doimo; Måns Andréasson; Valentin L’Hôte; Erik Chorell; Sjoerd Wanrooij
• Keywords: Conjugate; Chemical Biology; Derivative (finance); BODIPY

G-quadruplex (G4) DNA structures are implicated in central biological processes and considered promising therapeutic targets because of their links to human diseases such as cancer. However, functional details how, when, why G4 form vivo largely missing leaving a knowledge gap that requires tailored chemical biology studies relevant live-cell model systems. Towards this end, we developed synthetic platform generate complementary probes centered around one the most effective selective stabilizing compounds, Phen-DC3. We used structure-based design substantial devlopments equip Phen-DC3 with an amine position does not interfere interactions. next reactive handle conjugate BODIPY fluorophore This generated fluorescent derivative retained selectivity, stabilization, cellular effect revealed localization function cells. To increase uptake, second probe conjugated cell-penetrating peptide was prepared using same amine-substituted derivative. The conjugation, while retaining selectivity increased nuclear effects, showcasing potential method modulate direct uptake e.g. delivery vehicles. applied approach multiple biochemical tools based on core structure can thus be advance uncover molecular approaches.