Browsing by Person "Burkhart, Ines"

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  • Research Data
    Exploring the modulation of the complex folding landscape of Human Telomeric DNA by low molecular weight ligands
    2025-02-04
    Burkhart, Ines 
    Schwalbe, Harald Jochen 
    Telomeric DNA forms G-quadruplex (G4) structures. G4s are crucial for genomic stability and therapeutic targeting. Using time-resolved NMR and CD spectroscopies, we investigated how the ligand Phen-DC3 modulates the folding of the human telomeric repeat 23TAG DNA sequence into G4. The kinetics are modulated by the ligand and by the presence of potassium cations (K+). Ligand binding to G4 occurs via a triphasic process with fast and slow phases. Notably, for the G4 structure in the presence of K+, the slow rate is ten times slower than without K+. These findings offer key insights into the modulation of the complex folding landscape of G4s by ligands, advancing our understanding of G4-ligand interactions for potential therapeutic applications.
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  • Research Data
    Structural Insights into Spare-Tire DNA G-Quadruplex from the Human VEGF Promoter
    2025-03-10
    Schwalbe, Harald Jochen 
    Burkhart, Ines 
    The vascular endothelial growth factor (VEGF) promoter region, which is involved in cancer progression, con-tains guanine-rich sequences capable of forming G-quadruplex (G4) structures. G4s play a critical role in transcriptional regulation and genomic stability and exhibit high structural polymorphism. The major VEGF G4 adopts a parallel topology involving the first four of five G-tracts (VEGF1234), while a potential "spare-tire" mechanism suggests the formation of VEGF1245 in response to oxidative damage. Here, we characterize this alternative G4 (VEGF1245), formed by excluding the third G-tract, using circular dichroism (CD) and nu-clear magnetic resonance (NMR) spectroscopy. Structural analysis reveals that VEGF1245 folds in a hybrid conformation. Different to other five tract containing G4s, for which various stand topologies can rapidly interconvert, VEGF1245 remains thermodynamically metastable and does not refold spontaneously into VEGF1234 at physiological temperatures. Further trapping of the VEGF1245 conformation by a photolabile protecting group and its in-situ release documents that the transition to VEGF1234 requires elevated tem-peratures, implicating kinetic barriers in the refolding process and the delineation of VEGF1245 as prominent metastable conformation. Our findings provide new insights into transcriptional regulation and DNA repair for the cancer-related VEGF-G4.
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