دورية أكاديمية
Structural Optimization of Azacryptands for Targeting Three‐Way DNA Junctions
| العنوان: | Structural Optimization of Azacryptands for Targeting Three‐Way DNA Junctions |
|---|---|
| المؤلفون: | Pipier, Angélique, Chetot, Titouan, Kalamatianou, Apollonia, Martin, Nicolas, Caroff, Maëlle, Britton, Sébastien, Chéron, Nicolas, Trantírek, Lukáš, Granzhan, Anton, Monchaud, David |
| المساهمون: | Institut de Chimie Moléculaire de l'Université de Bourgogne Dijon (ICMUB), Université de Bourgogne (UB)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS), Chimie et modélisation pour la biologie du cancer (CMBC), Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Masaryk University Brno (MUNI), ANR-22-CE44-0039,InJUNCTION,Des outils moléculaires pour l'étude des jonctions d'ADN(2022) |
| المصدر: | ISSN: 1433-7851. |
| بيانات النشر: | HAL CCSD Wiley-VCH Verlag |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | DNA junctions, ligands, in vitro assays, molecular dynamics, NMR, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | International audience ; Transient melting of the duplex‐DNA (B‐DNA) during DNA transactions allows repeated sequences to fold into non‐B DNA structures, including DNA junctions and G‐quadruplexes. These noncanonical structures can act as impediments to DNA polymerase progression along the duplex, thereby triggering DNA damage and ultimately jeopardizing genomic stability. Their stabilization by ad hoc ligands is currently being explored as a putative anticancer strategy since it might represent an efficient way to inflict toxic DNA damage specifically to rapidly dividing cancer cells. The relevance of this strategy is only emerging for three‐way DNA junctions (TWJs) and, to date, no molecule has been recognized as a reference TWJ ligand, featuring both high affinity and selectivity. Herein, we characterize such reference ligands through a combination of in vitro techniques comprising affinity and selectivity assays (competitive FRET‐melting and TWJ Screen assays), functional tests (qPCR and Taq stop assays), and structural analyses (molecular dynamics and NMR investigations). We identify novel azacryptands TrisNP‐amphi and TrisNP‐ana as the most promising ligands, interacting with TWJs with high affinity and selectivity. These ligands represent new molecular tools to investigate the cellular roles of TWJs and explore how they can be exploited in innovative anticancer therapies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-04618018; https://hal.science/hal-04618018Test; https://hal.science/hal-04618018/documentTest; https://hal.science/hal-04618018/file/Pipier%20et%20al%20-%20Personal%20copy.pdfTest |
| DOI: | 10.1002/anie.202409780 |
| الإتاحة: | https://doi.org/10.1002/anie.202409780Test https://hal.science/hal-04618018Test https://hal.science/hal-04618018/documentTest https://hal.science/hal-04618018/file/Pipier%20et%20al%20-%20Personal%20copy.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.E2FDFDC0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/anie.202409780 |
|---|