Article
Chemistry, Analytical
Minghong Jian, Hua Zhang, Xiaotong Li, Zhenxin Wang
Summary: A novel peptide microarray-based fluorescence assay was proposed to profile multiple MMPs activities during the progression of osteosarcoma. This method demonstrated excellent selectivity and sensitivity in detecting cellular secreted MMPs, with the potential to reveal the relationship between MMP activity pattern in serum and disease progression and tumor type.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Chemistry, Medicinal
Theresa Kircher, Tatu Pantsar, Andreas Oder, Jens Peter von Kries, Michael Juchum, Bent Pfaffenrot, Philip Kloevekorn, Wolfgang Albrecht, Roland Selig, Stefan Laufer
Summary: MKK4 plays a key role in liver regeneration, making new small molecules inhibiting MKK4 potential candidates for treating acute and chronic liver diseases. Optimization of compound design led to the selection of fluorescent compounds with high binding affinities, with compound 45 identified as a suitable tool for studying new small-molecule inhibitors of MKK4.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Riet Hilhorst, Adrienne van den Berg, Piet Boender, Tom van Wezel, Tim Kievits, Rik de Wijn, Rob Ruijtenbeek, Willem E. Corver, Hans Morreau
Summary: STK activity profiling can accurately differentiate benign and malignant thyroid tumors and generate unbiased hypotheses regarding differentially active kinases. This approach can serve as a model for selecting novel kinase inhibitors for the treatment of recurrent thyroid and other cancers.
Article
Biophysics
Minghong Jian, Xudong Sun, Hua Zhang, Xiaotong Li, Shasha Li, Zhenxin Wang
Summary: Matrix metalloproteinases (MMPs) are attractive biomarkers for cancer diagnosis and treatment, but their low abundance in biological samples, especially in the early stages of tumors, makes it challenging to precisely analyze MMP activities. In this study, a peptide microarray-based metal-enhanced fluorescence assay (PMMEFA) is proposed as a sensitive and specific method to simultaneously detect MMP-1, -2, -3, -7, -9, and -13 activities. The PMMEFA showed excellent sensitivity and was capable of detecting MMP activities in various matrices.
BIOSENSORS & BIOELECTRONICS
(2024)
Article
Medicine, Research & Experimental
James Austerberry, John Edwards, Tim Eyes, Jeremy P. Derrick
Summary: The method involves using a synthetic peptide microarray to study the binding behavior of therapeutic proteins under different solution conditions. By analyzing peptide adhesion profiles, quantitative relationships between solution conditions can be established, enabling comparisons of monoclonal antibodies. Machine learning methods, such as neural networks, can be applied to train data on indicators of protein stability and self-association, providing insights into therapeutic protein formulation.
MOLECULAR PHARMACEUTICS
(2021)
Review
Chemistry, Analytical
Saimon M. M. Silva, Miaosi Li, Alexandre Xavier Mendes, Simon E. E. Moulton
Summary: The use of reagentless protein-based biosensors has the potential to revolutionize our understanding of biology and personalized health monitoring by directly monitoring molecular analytes in bodily fluids. Currently available molecular sensors are limited in their applicability to relevant biomarkers due to their reliance on specific enzymatic or chemical reactivity. A new class of reagentless protein-based electrochemical sensors has been introduced to overcome this limitation and enable direct measurements of biomarkers in unprocessed biological fluids. This mini-review discusses recent advances in the development of electroanalytical modular biosensors that integrate all the necessary components for autonomous functionality.
Article
Chemistry, Analytical
Satoshi Okada, Yuka Muto, Bo Zhu, Hiroshi Ueda, Hiroyuki Nakamura
Summary: Researchers have developed a fluorescent peptide sensor called 26-Dan for the highly sensitive and convenient detection of SARS-CoV-2. This sensor is adaptable to virus variants and, when combined with a portable microfluidic fluorescence polarization analyzer, can detect the virus within 3 minutes. This study represents a promising step towards a rapid and convenient test for SARS-CoV-2 and other potential pandemic-prone diseases.
ANALYTICAL CHEMISTRY
(2023)
Article
Infectious Diseases
Shuai-Bing Dong, Di Xiao, Jing-Yao Liu, Hui-Mei Bi, Zun-Rong Zheng, Li-Da Wang, Xiao-Wen Yang, Guo-Zhong Tian, Hong-Yan Zhao, Dong-Ri Piao, Zhi-Feng Xing, Hai Jiang
Summary: This study evaluated the value of Fluorescence Polarization Immunoassay (FPA) for the diagnosis of human brucellosis in China by recruiting 320 suspected cases. FPA showed high diagnostic value with a cutoff value of 88.5 mP, and when combined with ELISA, the sensitivity of diagnosis was significantly improved. FPA may have potential as a diagnostic method for human brucellosis in China.
INFECTIOUS DISEASES OF POVERTY
(2021)
Article
Multidisciplinary Sciences
Jie Zhong, Yuegui Guo, Shaoyong Lu, Kun Song, Ying Wang, Li Feng, Zhen Zheng, Qiufen Zhang, Jiacheng Wei, Peng Sang, Yan Shi, Jianfeng Cai, Guoqiang Chen, Chen-Ying Liu, Xiuyan Yang, Jian Zhang
Summary: This study identifies a best-in-class inhibitor for the protein-protein interaction crucial to colorectal cancer metastasis and develops a sensitivity-enhanced tracer for fluorescence polarization assays to accurately detect high-activity inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Analytical
Xueqing Tao, Wei Zou, Yan Qin, Chunyi Tong, Bin Liu
Summary: By designing a peptide probe and reduced graphene oxide, a new biosensing system was constructed for accurate detection and intracellular imaging of caspase-8 activity. The proposed method exhibited a linear response range and low detection limit in vitro, and successfully monitored the upregulation of intracellular caspase-8 activity.
Article
Biophysics
Hanjun Cheng, Zhonghan Li, Zhili Guo, Shiqun Shao, Li Mo, Wei Wei, Min Xue
Summary: An analytical method was developed to detect D2HG levels in single cancer cells using cascade enzymatic reactions on a resazurin-based fluorescence reporter. The method demonstrated high selectivity and sensitivity towards D2HG, allowing for the identification of effective combination targeted therapy against IDH-mutant glioma cells through single-cell profiling. The results revealed complex interplays between metabolic and oncogenic signaling pathways.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Chemistry, Medicinal
Maho Takioku, Yuta Takamura, Michiko Fujihara, Masaki Watanabe, Shoya Yamada, Mayu Kawasaki, Sohei Ito, Shogo Nakano, Hiroki Kakuta
Summary: This study found that RXR antagonist CBTF-EE may bind in different modes depending on the presence of nitrobenzoxadiazole or boron-dipyrromethene fluorophores at the end of the alkoxy chain. Fluorescence assays and docking simulations supported the conclusion that the binding modes of these compounds varied.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Katja F. Hellendahl, Maryke Fehlau, Sebastian Hans, Peter Neubauer, Anke Kurreck
Summary: The study introduces a luciferase-based assay for the detection of NK activity, which was validated in a 96-well plate format. The high-throughput assay showed comparable results to HPLC analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Carmen Mihaela Tilmaciu, Bhimareddy Dinesh, Morgan Pellerano, Sebastien Diot, Melanie Guidetti, Julien Vollaire, Alberto Bianco, Cecilia Menard-Moyon, Veronique Josserand, May C. Morris
Summary: The novel CDK1 activity reporter, utilizing the sensitivity of a fluorescent biosensor and the properties of carbon nanotubes, allows for sensitive and dose-dependent measurement of CDK1 activity, monitoring of intracellular kinases, and direct fluorescence imaging within tumor xenografts in mice.
Article
Chemistry, Analytical
Fabian O. Romero-Soto, Laura Weber, Dario Mager, Mohammad Mahdi Aeinehvand, Sergio O. Martinez-Chapa
Summary: The pumping mechanism in centrifugal microfluidic platforms allows liquid delivery against the unidirectional centrifugal force. The electrolysis pump relies on pneumatic pressure generated by the accumulation of oxygen and hydrogen to propel liquids towards the center of the disc. In this study, the performance of the electrolysis pump at low power ranges and its applications in real-life scenarios were analyzed and demonstrated.
SENSORS AND ACTUATORS B-CHEMICAL
(2023)
Article
Biochemistry & Molecular Biology
Hany S. Ibrahim, Mohamed Abdelsalam, Yanira Zeyn, Matthes Zessin, Al-Hassan M. Mustafa, Marten A. Fischer, Patrik Zeyen, Ping Sun, Emre F. Buelbuel, Anita Vecchio, Frank Erdmann, Matthias Schmidt, Dina Robaa, Cyril Barinka, Christophe Romier, Mike Schutkowski, Oliver H. Kraemer, Wolfgang Sippl
Summary: In this study, a novel series of selective Class I HDAC inhibitors were synthesized and tested in vitro and in vivo. The most potent compound showed strong inhibitory effects and potential for treating various types of blood cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Ehab Ghazy, Mohamed Abdelsalam, Dina Robaa, Raymond J. Pierce, Wolfgang Sippl
Summary: This review focuses on the recent development of inhibitors for schistosome histone deacetylases, particularly inhibitors of Schistosoma mansoni histone deacetylase 8, which have shown promise for the treatment of schistosomiasis.
Article
Biochemistry & Molecular Biology
Emre F. Bulbul, Jelena Melesina, Hany S. Ibrahim, Mohamed Abdelsalam, Anita Vecchio, Dina Robaa, Matthes Zessin, Mike Schutkowski, Wolfgang Sippl
Summary: In this study, a computational approach was used to predict the selectivity of inhibitors targeting HDAC1, HDAC2, and HDAC3. The developed binding free-energy models showed significant correlation between binding free energy and in vitro inhibitory activities, and successfully predicted the efficacy of newly designed inhibitors.
Article
Biochemistry & Molecular Biology
Diana Kalbas, Marat Meleshin, Sandra Liebscher, Matthes Zessin, Jelena Melesina, Cordelia Schiene-Fischer, Emre Fatih Bu''lbu''l, Frank Bordusa, Wolfgang Sippl, Mike Schutkowski
Summary: Sirtuins are protein deacylases involved in regulating metabolism, stress responses, and aging-related diseases. In this study, we synthesized and characterized 3-aryl-mercaptobutyrylated peptide derivatives as effective and selective Sirtuin 2 inhibitors. Our findings suggest that these inhibitors bind to the selectivity pocket of Sirtuin 2, inducing a rearrangement of the active site. Interestingly, 3-aryl-mercapto-nonalyl or palmitoyl derivatives exhibited a different binding mode, blocking both the hydrophobic channel and the nicotinamide pocket.
Article
Biochemistry & Molecular Biology
Salma Darwish, Ehab Ghazy, Tino Heimburg, Daniel Herp, Patrik Zeyen, Rabia Salem-Altintas, Johannes Ridinger, Dina Robaa, Karin Schmidtkunz, Frank Erdmann, Matthias Schmidt, Christophe Romier, Manfred Jung, Ina Oehme, Wolfgang Sippl
Summary: This study developed proteolysis targeting chimeras (PROTACs) of HDAC8 based on potent and selective HDAC8 inhibitors. The selective HDAC8 PROTACs showed anti-neuroblastoma activity in cells, indicating their potential as targeted therapy for neuroblastoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Hazem Ahmed, Livio Gisler, Nehal H. Elghazawy, Claudia Keller, Wolfgang Sippl, Steven H. Liang, Ahmed Haider, Simon M. Ametamey
Summary: GluN2B-enriched NMDARs are associated with several neurodegenerative and psychiatric diseases. In this study, a tritium-labeled form of OF-NB1 was developed as a selective GluN1/2B PET imaging agent. Competitive binding experiments and molecular simulations demonstrated the superior selectivity and performance of OF-NB1, making it a promising tool for screening potential GluN1/2B drug candidates.
Article
Chemistry, Organic
Mohamed Abdelsalam, Matthes Zessin, Matthias Schmidt, Mike Schutkowski, Wolfgang Sippl
Summary: The design and synthesis of a selective degrader of histone deacetylase-3 (HDAC3) using proteolysis targeting chimeras (PROTACs) is described in this study. The newly synthesized compound showed good inhibitory activity against HDAC3 but did not exhibit degradation for the targeted HDACs.
Editorial Material
Biochemistry & Molecular Biology
Wolfgang Sippl
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Mohamed Abdelsalam, Mariia Zmyslia, Karin Schmidtkunz, Anita Vecchio, Sebastian Hilscher, Hany S. Ibrahim, Mike Schutkowski, Manfred Jung, Claudia Jessen-Trefzer, Wolfgang Sippl
Summary: In this study, a series of prodrugs for class I histone deacetylases (HDACs) were designed and synthesized using known selective HDAC inhibitors. Compound 6 showed the most potent inhibitory activity against nitroreductase (NTR)-transfected leukemic cells.
ARCHIV DER PHARMAZIE
(2023)
Article
Oncology
Ramy Ashry, Al-Hassan M. Mustafa, Kristin Hausmann, Michael Linnebacher, Susanne Strand, Wolfgang Sippl, Matthias Wirth, Oliver H. Kraemer
Summary: Tumors in the pancreas and colon are still a clinical challenge. Different gene expression profiles between cancer cells and normal cells can be targeted by drugs that modulate protein acetylation. KH16 is a novel compound that induces hyperacetylation, leading to cell death in tumor cells while sparing normal cells. It shows superior efficacy compared to clinically established drugs. Further studies can focus on KH16 and similar compounds for cancer therapy.
Article
Chemistry, Medicinal
Emre F. F. Buelbuel, Dina Robaa, Ping Sun, Fereshteh Mahmoudi, Jelena Melesina, Matthes Zessin, Mike Schutkowski, Wolfgang Sippl
Summary: This study analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have shown promising effects in various cancer cell lines. The created models, including pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models, explain in vitro data well and were used to develop novel HDAC3 inhibitors.
Article
Biology
Fady Baselious, Dina Robaa, Wolfgang Sippl
Summary: In this study, we optimized the HDAC11 AlphaFold model by adding the catalytic zinc ion and successfully generated stable complexes for docking of selective inhibitors. The most reasonable pose was selected based on structural comparison, and the model explained the binding behavior of known HDAC11 inhibitors.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Review
Chemistry, Multidisciplinary
Conrad V. Simoben, Smith B. Babiaka, Aurelien F. A. Moumbock, Cyril T. Namba-Nzanguim, Donatus Bekindaka Eni, Jose L. Medina-Franco, Stefan Guenther, Fidele Ntie-Kang, Wolfgang Sippl
Summary: The use of traditional medicine has a long history and is still relied upon by many, especially in developing or underprivileged communities. In silico-based methods have played a crucial role in drug discovery, particularly in identifying natural product-based candidates. However, there are challenges in identifying and proposing novel natural product-based hits.
