المؤلفون: Qiu, Dehui, He, Fangni, Liu, Yuan, Zhou, Zhaoxi, Yang, Yuqin, Long, Zhongwen, Chen, Qianqian, Chen, Desheng, Wei, Shijiong, Mao, Xuanxiang, Zhang, Xiaobo, Mergny, Jean‐louis, Monchaud, David, Ju, Huangxian, Zhou, Jun

المساهمون: Nanjing University (NJU), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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)

المصدر: ISSN: 2198-3844 ; Advanced Science ; https://hal.science/hal-04625285Test ; Advanced Science, 2024, ⟨10.1002/advs.202402237⟩.

مصطلحات موضوعية: Artificial enzyme hemin histidine analogue G-quadruplex, Artificial enzyme, hemin, histidine analogue, G-quadruplex, [CHIM]Chemical Sciences

الوصف: International audience ; Abstract Nanomaterials excel in mimicking the structure and function of natural enzymes while being far more interesting in terms of structural stability, functional versatility, recyclability, and large‐scale preparation. Herein, the story assembles hemin, histidine analogs, and G‐quadruplex DNA in a catalytically competent supramolecular assembly referred to as assembly‐activated hemin enzyme (AA‐heminzyme). The catalytic properties of AA‐heminzyme are investigated both in silico (by molecular docking and quantum chemical calculations) and in vitro (notably through a systematic comparison with its natural counterpart horseradish peroxidase, HRP). It is found that this artificial system is not only as efficient as HRP to oxidize various substrates (with a turnover number k cat of 115 s −1) but also more practically convenient (displaying better thermal stability, recoverability, and editability) and more economically viable, with a catalytic cost amounting to <10% of that of HRP. The strategic interest of AA‐heminzyme is further demonstrated for both industrial wastewater remediation and biomarker detection (notably glutathione, for which the cost is decreased by 98% as compared to commercial kits).

العلاقة: hal-04625285; https://hal.science/hal-04625285Test; https://hal.science/hal-04625285/documentTest; https://hal.science/hal-04625285/file/Personal%20copy.pdfTest

الإتاحة: https://doi.org/10.1002/advs.202402237Test
https://hal.science/hal-04625285Test
https://hal.science/hal-04625285/documentTest
https://hal.science/hal-04625285/file/Personal%20copy.pdfTest

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.

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.

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

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

المؤلفون: Mitteaux, Jérémie, Raevens, Sandy, Wang, Zi, Pirrotta, Marc, Valverde, Ibai, E, Hudson, Robert, H E, 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)

المصدر: ISSN: 1359-7345.

مصطلحات موضوعية: [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.GEN]Life Sciences [q-bio]/Genetics

الوصف: International audience ; The ability of the phenylpyrrolocytosine (PhpC) small molecule to unfold G-quadruplex (G4) nucleic acids in human cells is demonstrated here both qualitaOvely and quanOtaOvely.

العلاقة: hal-04391014; https://hal.science/hal-04391014Test; https://hal.science/hal-04391014/documentTest; https://hal.science/hal-04391014/file/CC2024%20-%20personal%20copy%20DM.pdfTest

الإتاحة: https://doi.org/10.1039/D3CC05155BTest
https://hal.science/hal-04391014Test
https://hal.science/hal-04391014/documentTest
https://hal.science/hal-04391014/file/CC2024%20-%20personal%20copy%20DM.pdfTest

المؤلفون: Monchaud, David

مصطلحات موضوعية: Quantitative Biology - Biomolecules, Quantitative Biology - Subcellular Processes

الوصف: DNA and RNA quadruplexes are extensively studied for the key roles they are suspected to play in the cellular regulation networks at both genomic and transcriptomic levels. The reliable detection of quadruplexes in cells was and remains a challenging task. Here, we describe the various strategies that have been implemented over the past years to visualize functionally relevant DNA and RNA quadruplexes in human cells, from immunodetection studies to the design and use of quadruplex-specific turn-on fluorescent probes.
Comment: Review, 28 pages, 10 figures, 135 references

الوصول الحر: http://arxiv.org/abs/1910.07023Test

المؤلفون: Sassi, Aicha, Fredon, Maxime, Cotte, Alexia, K, Fuselier, Camille, Schneider, Christophe, Martiny, Laurent, Monchaud, David, Chekir-Ghedira, Leila, Aires, Virginie, Delmas, Dominique

المساهمون: Lipides - Nutrition - Cancer Dijon - U1231 (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Matrice Extracellulaire et Dynamique Cellulaire - UMR CNRS 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), 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), Université de Monastir - University of Monastir (UM), Centre Régional de Lutte contre le cancer Georges-François Leclerc Dijon (UNICANCER/CRLCC-CGFL), UNICANCER

المصدر: ISSN: 2073-4409 ; Cells ; https://hal.science/hal-04124055Test ; Cells, 2023, 12 (12), pp.1561. ⟨10.3390/cells12121561⟩.

مصطلحات موضوعية: chrysin, cancer, melanoma, chemoprevention, DNA damage, angiogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology

الوصف: International audience ; Despite the progress made in treatments, melanoma is one of the cancers for which its incidence and mortality have increased during recent decades. In the research of new therapeutic strategies, natural polyphenols such as chrysin could be good candidates owing to their capacities to modulate the different fundamental aspects of tumorigenesis and resistance mechanisms, such as oxidative stress and neoangiogenesis. In the present study, we sought to determine whether chrysin could exert antitumoral effects via the modulation of angiogenesis by acting on oxidative stress and associated DNA damage. For the first time, we show a link between chrysin-induced antiproliferative effects, the activation of the DNA damage pathway, and its ability to limit angiogenesis. More specifically, herein, we show that chrysin induces single-and double-stranded DNA breaks via the activation of the DNA damage response pathway: ATM (ataxia-telangiectasia-mutated)/Chk2 (checkpoint kinase 2) and ATR (ataxia telangiectasia and Rad3-related)/Chk1 (checkpoint kinase 1) pathways. Strong activation of this DNA damage response was found to be partly involved in the ability of chrysin to limit angiogenesis and may partly involve a direct interaction between the polyphenol and DNA G-quadruplex structures responsible for the replication fork collapse. Moreover, these events were associated with a marked reduction in melanoma cells' capacity to secrete proangiogenic factor VEGF-A. The disruption of these key protein actors in tumor growth by chrysin was also confirmed in a syngeneic model of B16 melanoma. This last point is of importance to further consider the use of chrysin as a new therapeutic strategy in melanoma treatment.

العلاقة: hal-04124055; https://hal.science/hal-04124055Test; https://hal.science/hal-04124055/documentTest; https://hal.science/hal-04124055/file/Cells%20-%202023%20-%2012%20-%201561.pdfTest

الإتاحة: https://doi.org/10.3390/cells12121561Test
https://hal.science/hal-04124055Test
https://hal.science/hal-04124055/documentTest
https://hal.science/hal-04124055/file/Cells%20-%202023%20-%2012%20-%201561.pdfTest

المؤلفون: Zhang, Xiaobo, Qiu, Dehui, Chen, Jielin, Zhang, Yue, Wang, Jiawei, Chen, Desheng, Liu, Yuan, Cheng, Mingpan, Monchaud, David, Mergny, Jean-Louis, Ju, Huangxian, Zhou, Jun

المساهمون: Nanjing University (NJU), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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)

المصدر: ISSN: 0002-7863.

مصطلحات موضوعية: [CHIM.CATA]Chemical Sciences/Catalysis

الوصف: International audience ; Chimeric peptide-DNAzyme (CPDzyme) is a novel design of an artificial peroxidase that relies on the covalent assembly of DNA (quadruplex-DNA, or G4), peptides and an enzyme cofactor (hemin) in a single scaffold. An accurate control of the assembly of these different partners allows for the design of the efficient CPDzyme prototype G4-Hemin-KHRRH, found to be >2,000-fold more active (in terms of conversion number kcat) than the corresponding but non-covalent complex and, more importantly, >1.5-fold active than the corresponding native peroxidase (horseradish peroxidase, or HRP) when considering a single catalytic center. This unique performance originates in a series of improvements gradually made thanks to an accurate selection and arrangement of the different components of the CPDzyme, in order to benefit from synergistic interactions between them. The optimized prototype G4-Hemin-KHRRH is efficient and robust as it can be used under a wide range of non-physiologically relevant conditions (organic solvents, high temperature (95°C), in a wide range of pH (from 2 to 10)), thus compensating for the shortcomings of natural enzymes. Our approach thus opens broad prospects for the design of ever more efficient artificial enzymes.

العلاقة: hal-03995188; https://hal.science/hal-03995188Test; https://hal.science/hal-03995188/documentTest; https://hal.science/hal-03995188/file/CPDzyme%20-%20personnal%20copy.pdfTest

الإتاحة: https://doi.org/10.1021/jacs.2c11318Test
https://hal.science/hal-03995188Test
https://hal.science/hal-03995188/documentTest
https://hal.science/hal-03995188/file/CPDzyme%20-%20personnal%20copy.pdfTest

المؤلفون: Mao, Xuanxiang, Zhang, Xiaobo, Chao, Zhicong, Qiu, Dehui, Wei, Shijiong, Luo, Rengan, Chen, Desheng, Zhang, Yue, Chen, Yun, Yang, Yuanjiao, Monchaud, David, Ju, Huangxian, Mergny, Jean‐louis, Lei, Jianping, Zhou, Jun

المساهمون: Nanjing University (NJU), 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), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-20-CE12-0023,G4Access,Role des G-quadruplexes dans la régulation transcriptionnelle(2020)

المصدر: ISSN: 2192-2640.

مصطلحات موضوعية: G-quadruplex, G-quadruplex/hemin, upconverted metal-organic framework, photodynamic therapy, antiproliferative activity, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer

الوصف: International audience ; Given the complexity of the tumor microenvironment, multiple strategies are being explored to tackle hypoxic tumors. One of the most efficient strategies combines several therapeutic modalities and typically requires the development of multifunctional nanocomposites through sophisticated synthetic procedures. Here, the G-quadruplex (G4)-forming sequence AS1411-A (d-(G2T)4TG(TG2)4A) was designed and used for its anti-tumor and biocatalytic properties, such as increasing the production of O2 ca. 2fold as compared to the parent AS1411 sequence. Subsequently, the AS1411-A/hemin complex (GH) was grafted on the surface and pores of a core-shell upconverted metalorganic framework (UMOF) to generate a UMGH nanoplatform. Compared with UMOF, UMGH exhibited enhanced colloidal stability, increased targeting of tumor cells and improved O2 production (8.5-fold) in situ. When irradiated with near-infrared (NIR) light, the UMGH antitumor properties were bolstered by photodynamic therapy (PDT), thanks to its ability to convert O2 into singlet oxygen (1 O2). Combined with the antiproliferative activity of AS1411-A, this novel approach herein lays the foundation for a new type of G4-based nanomedicine.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37402245; hal-04152890; https://hal.science/hal-04152890Test; https://hal.science/hal-04152890v2/documentTest; https://hal.science/hal-04152890v2/file/Adv%20Healthc%20Mat%20-%202023%20-%20Personal%20copy.pdfTest; PUBMED: 37402245

الإتاحة: https://doi.org/10.1002/adhm.202300561Test
https://hal.science/hal-04152890Test
https://hal.science/hal-04152890v2/documentTest
https://hal.science/hal-04152890v2/file/Adv%20Healthc%20Mat%20-%202023%20-%20Personal%20copy.pdfTest

المؤلفون: Qiu, Dehui, Cheng, Mingpan, Stadlbauer, Petr, Chen, Jielin, Langer, Michal, Zhang, Xiaobo, Gao, Qiang, Ju, Huangxian, Šponer, Jiří, Mergny, Jean-Louis, Monchaud, David, Zhou, Jun

المساهمون: Nanjing University (NJU), China Pharmaceutical University (CPU), Institute of Biophysics of the Czech Academy of Sciences (IBP / CAS), Czech Academy of Sciences Prague (CAS), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), ANR-21-CE44-0005,iCARE,Pertinence biologique et ciblage de l'ADN i-motif(2021)

المصدر: ISSN: 2155-5435.

مصطلحات موضوعية: DNAzyme, Holliday junction, molecular dynamics simulations, catalytic mechanism, [CHIM.CATA]Chemical Sciences/Catalysis, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry

الوصف: International audience ; The nature, composition, and topology of the active sites of both natural and artificial enzymes are key determinants of their catalytic performance. While interesting structural insights have been obtained for natural enzymes (e.g., horseradish peroxidase, HRP), the accurate catalytic microenvironment of HRP-mimicking DNA-based catalysts known as G-quadruplex (GQ)/hemin DNAzymes is still unclear. Herein, we report on a strategy allowing for fully controlling the nature of the active site of GQ DNAzyme, precisely manipulating the composition and topology of the hemin (Fe(III)protoporphyrin IX) cofactor binding site. This was achieved by introducing GQ within a Holliday junction (HJ) suprastructure that enables to seize control of both the GQ folding topology (parallel, antiparallel, hybrid) and the GQ strand directionality (clockwise, counterclockwise). By doing so, we demonstrate that the different GQ topologies are equivalent for both hemin binding and activation and that the flanking nucleotides (dA or dTC) modulate the activation of hemin in a GQ topology-dependent manner. Our experimental findings are supported by the most extensive molecular dynamics simulations ever been done on GQ DNAzyme, thus providing unique mechanistic insights into the biocatalytic activity of GQs.

العلاقة: hal-04175036; https://hal.science/hal-04175036Test; https://hal.science/hal-04175036/documentTest; https://hal.science/hal-04175036/file/ACS%20Catal%20-%202023%20-%20Personal%20copy.pdfTest

الإتاحة: https://doi.org/10.1021/acscatal.3c02818Test
https://hal.science/hal-04175036Test
https://hal.science/hal-04175036/documentTest
https://hal.science/hal-04175036/file/ACS%20Catal%20-%202023%20-%20Personal%20copy.pdfTest

المؤلفون: 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)

المصدر: ISSN: 0001-4842.

مصطلحات موضوعية: [SDV]Life Sciences [q-bio], [CHIM]Chemical Sciences

الوصف: International audience

العلاقة: hal-03956357; https://hal.science/hal-03956357Test; https://hal.science/hal-03956357/documentTest; https://hal.science/hal-03956357/file/ACR%202023%20-%20Personal%20copy.pdfTest

الإتاحة: https://doi.org/10.1021/acs.accounts.2c00757Test
https://hal.science/hal-03956357Test
https://hal.science/hal-03956357/documentTest
https://hal.science/hal-03956357/file/ACR%202023%20-%20Personal%20copy.pdfTest

المؤلفون: 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)

المصدر: ISSN: 1097-2765.

مصطلحات موضوعية: [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]

الوصف: International audience ; Roschdi et al. report on a new higher-order RNA structure folding from an alternating uridine (U)/guanosine (G) repeated sequence-the pUG tail-into a peculiar G-quadruplex structurethe pUG fold-found to orchestrate the gene-silencing activity of pUGylated RNAs.

العلاقة: hal-03971075; https://hal.science/hal-03971075Test; https://hal.science/hal-03971075/documentTest; https://hal.science/hal-03971075/file/MolCell%202023%20-%20Spotlight%20-%20Personal%20copy.pdfTest

الإتاحة: https://doi.org/10.1016/j.molcel.2022.12.010Test
https://hal.science/hal-03971075Test
https://hal.science/hal-03971075/documentTest
https://hal.science/hal-03971075/file/MolCell%202023%20-%20Spotlight%20-%20Personal%20copy.pdfTest