An organic molecular compound for in-situ identification of mitochondrial G-quadruplexes in live cells

Author(s):  
Xiaomeng Guo ◽  
Hongbo Chen ◽  
Yan Liu ◽  
Dawei Yang ◽  
Qian Li ◽  
...  

Emerging studies have shown that mitochondrial G-quadruplex plays a critical role in regulating mitochondrial gene replication and transcription, which makes it a promising target for the diagnosis and treatment of...

2021 ◽  
Author(s):  
Xiaoyun Zhang ◽  
Jochen Spiegel ◽  
Sergio Martínez Cuesta ◽  
Santosh Adhikari ◽  
Shankar Balasubramanian

AbstractDNA–protein interactions regulate critical biological processes. Identifying proteins that bind to specific, functional genomic loci is essential to understand the underlying regulatory mechanisms on a molecular level. Here we describe a co-binding-mediated protein profiling (CMPP) strategy to investigate the interactome of DNA G-quadruplexes (G4s) in native chromatin. CMPP involves cell-permeable, functionalized G4-ligand probes that bind endogenous G4s and subsequently crosslink to co-binding G4-interacting proteins in situ. We first showed the robustness of CMPP by proximity labelling of a G4 binding protein in vitro. Employing this approach in live cells, we then identified hundreds of putative G4-interacting proteins from various functional classes. Next, we confirmed a high G4-binding affinity and selectivity for several newly discovered G4 interactors in vitro, and we validated direct G4 interactions for a functionally important candidate in cellular chromatin using an independent approach. Our studies provide a chemical strategy to map protein interactions of specific nucleic acid features in living cells.


2020 ◽  
pp. 71-74
Author(s):  
M.M. Melnyk ◽  
◽  
S.V. Nespradko ◽  
I.V. Goncharuk ◽  
M.V. Marchenko ◽  
...  

The objective: analyse the effectiveness of diagnosis and treatment for early cervical cancer. Materials and methods. Analysed 107 cases of women’s disease on CIN ІІІ, cancer in situ, they were on treatment in National cancer institute and Kyiv dictrict cancer dispensary from 2010 till 2015 years. Results. Diagnosed percent relapse CIN ІІІ, cancer in situ contain 4.57% uninvasive and invasive form – 0.94%. Conclusion. According diagnostic CIN ІІ and CIN ІІІ is recommended to do treatment conization and dynamic dispensary observation. Are making complex program of infection HPV16, 18. In appering of margins resection some elements of tumor after wider conization by forms of cancer in situ. Many of expansive burns in cervical glands, in making of reproductive function, going disease (nodel leiomyoma of corpus uteri etc). In perspective is accept the notion of looking after and screening research of considering infection HPV16, 18 on CIN І, CIN ІІ. Key words: cervical cancer, сancer in situ, CIN І–ІІІ, diagnostic, treatment, conization.


2021 ◽  
Vol 1157 ◽  
pp. 338394
Author(s):  
Xiao-Yue Tang ◽  
Yi-Ming Liu ◽  
Xiao-Lin Bai ◽  
Hao Yuan ◽  
Yi-Kao Hu ◽  
...  

2020 ◽  
Vol 59 (24) ◽  
pp. 9719-9726 ◽  
Author(s):  
Liu‐Yi Liu ◽  
Wenting Liu ◽  
Kang‐Nan Wang ◽  
Bo‐Chen Zhu ◽  
Xiao‐Yu Xia ◽  
...  

2006 ◽  
Vol 291 (6) ◽  
pp. F1123-F1132 ◽  
Author(s):  
James J. De Yoreo ◽  
S. Roger Qiu ◽  
John R. Hoyer

Calcium oxalate monohydrate (COM) is the primary constituent of the majority of renal stones. Osteopontin (OPN), an aspartic acid-rich urinary protein, and citrate, a much smaller molecule, are potent inhibitors of COM crystallization at levels present in normal urine. Current concepts of the role of site-specific interactions in crystallization derived from studies of biomineralization are reviewed to provide a context for understanding modulation of COM growth at a molecular level. Results from in situ atomic force microscopy (AFM) analyses of the effects of citrate and OPN on growth verified the critical role of site-specific interactions between these growth modulators and individual steps on COM crystal surfaces. Molecular modeling investigations of interactions of citrate with steps and faces on COM crystal surfaces provided links between the stereochemistry of interaction and the binding energy levels that underlie mechanisms of growth modification and changes in overall crystal morphology. The combination of in situ AFM and molecular modeling provides new knowledge that will aid rationale design of therapeutic agents for inhibition of stone formation.


2021 ◽  
Author(s):  
Evangelos Bisyris ◽  
Eleni Zingkou ◽  
Golfo G Kordopati ◽  
Minos-Timotheos Matsoukas ◽  
Plato A. Magriotis ◽  
...  

We applied a new in silico approach for fishing protease-substrate motifs to design a kallirein 7 (KLK7)-specific phosphonate activity-based probe (ABP) to quantify the active KLK7 in situ. Epidermal application...


2016 ◽  
Vol 193 ◽  
pp. 99-112 ◽  
Author(s):  
Ling Zhang ◽  
Jens Ulstrup ◽  
Jingdong Zhang

DNA quadruplexes (qs) are a class of “non-canonical” oligonucleotides (OGNs) composed of stacked guanine (G) quartets stabilized by specific cations. Metal porphyrins selectively bind to G-qs complexes to form what is known as DNAzyme, which can exhibit peroxidase and other catalytic activity similar to heme group metalloenzymes. In the present study we investigate the electrochemical properties and the structure of DNAzyme monolayers on single-crystal Au(111)-electrode surfaces using cyclic voltammetry and scanning tunnelling microscopy under electrochemical potential control (in situ STM). The target DNAzyme is formed from a single-strand OGN with 12 guanines and iron(iii) porphyrin IX (hemin), and assembles on Au(111) through a mercapto alkyl linker. The DNAzyme monolayers exhibit a strong pair of redox peaks at 0.0 V (NHE) at pH 7 in acetate buffer, shifted positively by about 50 mV compared to free hemin weakly physisorbed on the Au(111)-electrode surface. The voltammetric hemin signal of DNAzyme is enhanced 15 times compared with that of hemin adsorbed directly on the Au(111)-electrode surface. This is indicative of both the formation of a close to dense DNAzyme monolayer and that hemin is strongly bound to the immobilized 12G-qs in well-defined orientation favorable for interfacial ET with a rate constant of 6.0 ± 0.4 s−1. This is supported by in situ STM which discloses single-molecule G-quartet structures with a size of 1.6 ± 0.2 nm.


2017 ◽  
Vol 129 (39) ◽  
pp. 11950-11954 ◽  
Author(s):  
Hong-Wen Liu ◽  
Ke Li ◽  
Xiao-Xiao Hu ◽  
Longmin Zhu ◽  
Qiming Rong ◽  
...  

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