Article
Biochemistry & Molecular Biology
Junnosuke Hatanaka, Yuki Hirose, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: In this study, we synthesized linear pyrrole-imidazole polyamides (PIPs) that can selectively bind to DNA. These linear PIPs have lower molecular weights compared to commonly used hairpin PIPs. The binding affinity of the PIPs to DNA was improved by modifying the N-terminus of the linear PIPs. These findings provide insights for the design of effective linear PIPs.
Review
Pharmacology & Pharmacy
Thangavel Vaijayanthi, Ganesh N. Pandian, Hiroshi Sugiyama
Summary: Research shows that small molecules targeting DNA and/or RNA are important in precision medicine as they have consistent bioactivity among patients. This review discusses the progress of sequence-specific DNA-binding pyrrole-imidazole polyamides (PIPs) in modulating the transcriptional status of target genes, and explores how conjugation with DNA alkylating agents, epigenetic modulators, and other drugs can improve their clinical utility.
ADVANCED THERAPEUTICS
(2023)
Article
Chemistry, Medicinal
Yuki Hirose, Shinsuke Sato, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: Compound 1 and its analogs 2-4 have been found to covalently bind to RUNX-binding sequences, inhibiting the binding of RUNX proteins to their target sites and suppressing cancer growth. Compound 3 showed the highest alkylation efficiency, specificity, and better anticancer effects against pancreatic cancer in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yuki Hirose, Tomo Ohno, Sefan Asamitsu, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: A cyclic pyrrole-imidazole polyamide (cPIP) was synthesized to bind to the abnormal expanded CAG/CTG repeat DNA sequences, showing high binding affinity and specificity for its target DNA sequence.
Article
Biochemical Research Methods
Brionna McGorman, Simon Poole, Miguel Vazquez Lopez, Andrew Kellett
Summary: The development of compounds that can selectively bind with non-canonical DNA structures has expanded in recent years. In this study, a multiplex fluorescent polyacrylamide gel electrophoresis (PAGE) and microscale thermophoresis (MST) assays were used to evaluate junction-binding compounds. The combination of PAGE and MST provided complementary results for the visualization of junction formation and the determination of binding affinity, and can aid in the discovery and design of new therapeutics.
Review
Chemistry, Analytical
Hamed Zahraee, Zahra Khoshbin, Fatemeh Mohammadi, Mansour Mashreghi, Khalil Abnous, Seyed Mohammad Taghdisi
Summary: Nucleic acids can form highly regular and complex structures at the nanoscale through self-assembly and programmability. The smallest type of junction, known as three-way junction (TWJ), can be formed by hybridizing three DNA or RNA strands. TWJ nanostructures provide multifunctional sites for biomolecular nanoarchitectures. This study discusses the achievements and future potential of TWJ-based biosensors, specifically aptasensors, for monitoring different targets.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Zhiqiang Sun, Tommy Stormberg, Shaun Filliaux, Yuri L. Lyubchenko
Summary: The study utilized three-way DNA junctions as DNA labels for determining the protein's location on DNA substrates in AFM images. High-speed AFM experiments revealed a high dynamic of nucleosomes which could spontaneously unravel and disassemble.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Analytical
Jingjing Ye, Jiaxi Gao, Weixiang Huang, Ruo Yuan, Wenju Xu
Summary: It is interesting to use the branched arms of three-way DNA junction (3WDJ) for modifying specific recognizing and/or sensing elements of multivariate analytes. In this study, a bivariate electrochemical biosensor was developed based on a functional 3WDJ, with two targeting DNA segments specific to SARS-CoV-2 as analyte models. The biosensor showed simplified detection, high sensitivity, and potentially more accurate electrochemical assay of multivariate targets.
SENSORS AND ACTUATORS B-CHEMICAL
(2023)
Article
Chemistry, Analytical
Yanan Zhou, Yan Zeng, Dun Zhang, Peng Qi, Yingwen Wang, Yue Xin, Yan Sun
Summary: We have developed a simple and highly sensitive method for detecting bacterial DNA. By utilizing target-aided self-assembly cycle amplification coupled with DNA-AgNCs/three-way DNA junction, we successfully detected target DNA at concentrations as low as 19.95 fM, with good selectivity and recovery rate.
SENSORS AND ACTUATORS B-CHEMICAL
(2023)
Article
Chemistry, Multidisciplinary
Hua Chai, Peng Miao
Summary: A novel electrochemical strategy combining strand displacement amplification and DNA nanostructures was developed for ultrasensitive detection of ctDNA, achieving a limit of detection as low as 48 amol/L. This proposed electrochemical biosensor shows great potential for clinical applications.
CHINESE CHEMICAL LETTERS
(2021)
Article
Biochemical Research Methods
Chunxu Yu, Siyan Zhou, Xin Zhao, Yidan Tang, Lina Wang, Baiyang Lu, Fanzheng Meng, Bingling Li
Summary: The nucleic acid testing technology has advanced in recent years, but there are still challenges in the clinical application of multiple nucleic acid assays, such as accuracy, speed, and cost. This paper introduces a three-way junction structure that can translate analytes of loop-mediated isothermal amplification to a catalytic hairpin assembly. With a well-optimized nucleic acid circuit, multiple and logical analysis can be easily achieved in a single reaction with high sensitivity and selectivity. The experimental results of clinical samples support the potential clinical application of this methodology.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Zishan Feng, Wei Zhang, Longjie Li, Bocheng Tu, Weicong Ye, Xiaofeng Tang, Hongbo Wang, Xianjin Xiao, Tongbo Wu
Summary: A new method for detecting low-abundance mutations was developed using a DNA three-way junction structure and optimization of an assistant strand. The method showed improved selectivity for mutant-type DNA and cost savings. The sensitivity and accuracy of the method were demonstrated in the detection of a human ovarian cancer-related gene mutation.
CHINESE CHEMICAL LETTERS
(2021)
Article
Chemistry, Analytical
Jung Ho Kim, Seokjoon Kim, Sung Hyun Hwang, Tae Hwi Yoon, Jung Soo Park, Eun Sung Lee, Jisu Woo, Ki Soo Park
Summary: Water and food contaminated by pathogens are major causes of diseases and deaths globally. A system is needed to control pathogen contamination and quickly detect and monitor target pathogens. The three-way junction-induced transcription amplification can detect target nucleic acids effectively.
Article
Engineering, Environmental
Q. Li, J. Xia, M. Zhou, S. Deng, H. Zhang, Z. Xie
Summary: Based on experimental results, it was found that the flow discharge ratio and connected angle have a significant effect on energy loss, while the effect of downstream water depth is not obvious. With an increase in lateral inflow discharge, both flow velocity and vortex structure are enhanced. Circular manholes can reduce local energy loss compared to square manholes.
WATER SCIENCE AND TECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wasif Al-Shareef, Yogev Brown, Christopher Bryan, Elena Shuvaeva, Shhadeh Bsoul, Raanan Greenman, Majdi M. Kabaha, Nikolai B. Ulyanov, Emmanuel Skordalakes, Yehuda Tzfati
Summary: Telomerase is composed of telomerase RNA and telomerase reverse transcriptase, which maintain chromosome end integrity by copying a template onto chromosome ends. Despite diversity in telomerase RNA sequence across fungi and mammals, structural motifs essential for telomerase function are conserved. Est2 interacts with specific RNA structures and mutations in these domains cause severe telomere shortening, highlighting the conservation and importance of these interactions for telomerase function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Chunlei Wu, Zhehong Cheng, Danyi Lu, Ke Liu, Yulian Cheng, Pengxin Wang, Yimin Zhou, Meiqing Li, Ximing Shao, Hongchang Li, Wu Su, Lijing Fang
Summary: Researchers discovered a simplified analogue of Coibamide A and designed two novel peptide-drug conjugates, with one showing better drug release in vitro and significant tumor growth suppression in mice-bearing human tumor xenografts, indicating great potential in cancer drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Meiqing Li, Danyi Lu, Yulian Cheng, Chunlei Wu, Jianchao Zhang, Wenli Shi, Zhihao Ding, Yanyan Li, Binghua Cheng, Xian Lin, Ximing Shao, Hongchang Li, Lijing Fang, Ke Liu, Wu Su
Summary: The newly developed drug molecule PIP-Ht targets the Aurora A gene promoter and shows potent inhibitory effects on tumor cell growth and proliferation in vitro and in vivo, demonstrating potential as an effective candidate for cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Nanoscience & Nanotechnology
Ximing Shao, Zhihao Ding, Wenhua Zhou, Yanyan Li, Zhibin Li, Haodong Cui, Xian Lin, Guoli Cao, Binghua Cheng, Haiyan Sun, Meiqing Li, Ke Liu, Danyi Lu, Shengyong Geng, Wenli Shi, Guofang Zhang, Qingle Song, Liang Chen, Guocheng Wang, Wu Su, Lintao Cai, Lijing Fang, David Tai Leong, Yang Li, Xue-Feng Yu, Hongchang Li
Summary: The study reveals a tumoricidal mechanism of black phosphorus nanomaterials where they directly affect the mitotic centrosome machinery by suppressing polo-like kinase 1, suggesting that nanomaterials can be applied in targeted cancer therapy with their intrinsic nano-bio properties.
NATURE NANOTECHNOLOGY
(2021)
Article
Biochemical Research Methods
Peter Stacey, Hannah Lithgow, Xiao Lewell, Agnieszka Konopacka, Stephen Besley, Georgina Green, Ryan Whatling, Robert Law, Sascha Roeth, Gopal P. Sapkota, Ian E. D. Smith, Glenn A. Burley, John Harling, Andrew B. Benowitz, Markus A. Queisser, Marcel Muelbaier
Summary: A novel phenotypic screening approach was utilized to identify E3 ligase binders and generate functional HaloPROTACs for the degradation of fusion proteins in living cells. This method offers an important tool for further development of PROTACs.
Article
Biochemistry & Molecular Biology
Clive R. Bagshaw, Jendrik Hentschel, Michael D. Stone
Summary: Telomerases are moderately processive reverse transcriptases that extend the 3' ends of linear chromosomes using an integral RNA template. The processivity values vary at different positions, with a characteristic strong band every 6th position in gel electrophoresis due to repeat nucleotides. This analysis reveals that higher product concentrations associated with a certain type of processivity arise from a stalling of nucleotide incorporation during translocation.
Article
Multidisciplinary Sciences
Archana G. Chavan, Jeffrey A. Swan, Joel Heisler, Cigdem Sancar, Dustin C. Ernst, Mingxu Fang, Joseph G. Palacios, Rebecca K. Spangler, Clive R. Bagshaw, Sarvind Tripathi, Priya Crosby, Susan S. Golden, Carrie L. Partch, Andy LiWang
Summary: The study successfully reconstructed a complete cyanobacterial circadian clock system in vitro, including the central oscillator, signal transduction pathways, downstream transcription factor, and promoter DNA. By monitoring the oscillations in real time with a fluorescence-based readout, the study revealed previously unknown mechanisms by which the circadian system of cyanobacteria maintains pace and rhythmicity under variable protein concentrations.
Article
Chemistry, Multidisciplinary
Lauren M. Reid, Ileana Guzzetti, Tor Svensson, Anna-Carin Carlsson, Wu Su, Tomas Leek, Lena von Sydow, Werngard Czechtizky, Marija Miljak, Chandra Verma, Leonardo De Maria, Jonathan W. Essex
Summary: Understanding the conformational ensembles of intrinsically disordered proteins and peptides (IDPs) in different biological environments is crucial for understanding their mechanisms and functional roles, as well as potential treatments for diseases. This study investigates the structural landscape of the PLP peptide using molecular simulation and experimental validation, and identifies the CHARMM36m and REST2 protocol as suitable for studying environment-specific IDP conformations.
Article
Chemistry, Organic
Emma Campbell, Andrea Taladriz-Sender, Olivia Paisley, Alan R. Kennedy, Jacob T. Bush, Glenn A. Burley
Summary: This paper describes a modular approach to prepare tri- and tetracyclic carbazoles via sequential [3 + 2] heteroannulation. The optimization of Pd-catalyzed Buchwald-Hartwig amination followed by C/N-arylation in a one-pot process is established. Mechanistic analyses have identified the origins of the chemo- and regioselective sequential control of both bond-forming steps. The substrate scope is demonstrated by the preparation of a range of tri- and tetracyclic carbazoles, including expedient access to several natural products and anti-cancer agents.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Analytical
Frank Wesche, Leonardo De Maria, Tomas Leek, Frank Narjes, James Bird, Wu Su, Werngard Czechtizky
Summary: Inhalation of peptides offers the advantage of targeting lung tissue directly, but they are often quickly metabolized in the lungs. An assay workflow has been developed to study the half-life and metabolites of peptides in lung tissue, guiding early stage respiratory drug discovery projects through chemical modifications of peptide hits.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Nanoscience & Nanotechnology
Carlos J. Bueno-Alejo, Marina Santana Vega, Amanda K. Chaplin, Chloe Farrow, Alexander Axer, Glenn A. Burley, Cyril Dominguez, Hesna Kara, Vasileios Paschalis, Sumera Tubasum, Ian C. Eperon, Alasdair W. Clark, Andrew J. Hudson
Summary: Single-molecule imaging is important for studying the behavior and interactions of biological molecules. However, the irreversible adsorption of components onto surfaces poses a challenge for precise sampling. Interferometric scattering microscopy (iSCAT) can detect the adsorption and desorption of unlabeled proteins on glass surfaces. A surface passivation method using high-density perfluoroalkane brushes allows for continuous monitoring of protein adsorption and desorption without irreversible binding.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Katharine E. Gilbert, Aini Vuorinen, Arron Aatkar, Peter Pogany, Jonathan Pettinger, Emma K. Grant, Joanna M. Kirkpatrick, Katrin Rittinger, David House, Glenn A. Burley, Jacob T. Bush
Summary: A comprehensive profiling of sulfur(VI) fluoride reactivity is presented, focusing on fragment binders and optimized probes. The reactivity profile of S-VI-Fs is demonstrated through live cell chemoproteomics. The studies provide insights into the hydrolytic stability, protein reactivity, and chemoproteomic utility of S-VI-Fs, offering a valuable guide for designing ligands containing S-VI-Fs and expanding the liganded proteome.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jiajia Zou, Ashley C. Stammers, Andrea Taladriz-Sender, Jamie M. Withers, Iain Christie, Marina Santana Vega, Badri L. Aekbote, William J. Peveler, David A. Rusling, Glenn A. Burley, Alasdair W. Clark
Summary: An orthogonal, noncovalent approach is presented for the assembly of higher-order DNA origami nanostructures. By incorporating perfluorinated tags into DNA origami tiles, their hierarchical assembly is controlled via fluorous-directed recognition. This integrated catch-and-latch approach combining fluorous effect with base-pairing specificity enables increased assembly efficiency and requires fewer DNA sequences, providing a cheap and efficient means for producing discrete superstructures in DNA nanotechnology.
Article
Chemistry, Analytical
Frank Wesche, Leonardo De Maria, Tomas Leek, Frank Narjes, James Bird, Wu Su, Werngard Czechtizky
Summary: Peptides and peptide drug conjugates are being used to treat pulmonary diseases, but they are susceptible to proteolytic cleavage. This study developed a high-throughput LC-HRMS protocol to determine enzymatic protease stability of peptides for inhaled administration. Testing of metabolic stability in lung fluid (BALF) was also conducted. The results showed significant differences compared to literature-derived estimates, indicating the need for experimental workflows to guide peptide optimization in drug discovery projects.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Frederik Peschke, Andrea Taladriz-Sender, Matthew J. Andrews, Allan J. B. Watson, Glenn A. Burley
Summary: This study demonstrates the use of glutathione (GSH) as a redox modulator to promote a copper-catalyzed (3+2) cycloaddition reaction between an ynamine and an azide. This unique GSH-mediated reactivity gradient is then utilized in the dual sequential bio-orthogonal labeling.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemical Research Methods
Karina Chan, Preethi Soundarya Sathyamurthi, Markus A. Queisser, Michael Mullin, Harry Shrives, Diane M. Coe, Glenn A. Burley
Summary: This manuscript presents a cell-targeted approach to degrade RIPK2 in HER2+ cell lines using an antibody-PROTAC conjugate. The study demonstrates the potential for cell-selective delivery of PROTAC scaffolds by engaging with signature extracellular proteins expressed on the surface of specific cell types.
BIOCONJUGATE CHEMISTRY
(2023)
