Article
Chemistry, Medicinal
Hao Zhang, John Ginn, Wenhu Zhan, Yi J. Liu, Annie Leung, Akinori Toita, Rei Okamoto, Tzu-Tshin Wong, Toshihiro Imaeda, Ryoma Hara, Takafumi Yukawa, Mayako Michino, Jeremie Vendome, Thijs Beuming, Kenjiro Sato, Kazuyoshi Aso, Peter T. Meinke, Carl F. Nathan, Laura A. Kirkman, Gang Lin
Summary: Malaria is a global health threat, with the parasite Plasmodium falciparum developing resistance to antimalarial drugs. The proteasome of the parasite has been identified as a potential target, and a potent inhibitor has been developed.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Francesca Alessandra Ambrosio, Giosue Costa, Maria Eugenia Gallo Cantafio, Roberta Torcasio, Francesco Trapasso, Stefano Alcaro, Giuseppe Viglietto, Nicola Amodio
Summary: Multiple myeloma (MM) is an aggressive and incurable disease, characterized by cycles of treatment, remission, and relapse. Proteasome inhibitors (PIs), such as Bortezomib, carfilzomib, and ixazomib, have become the gold standard for MM treatment, improving survival outcomes. Recent research has focused on natural compounds that can inhibit the proteasome, potentially leading to new anti-MM drugs.
Review
Pharmacology & Pharmacy
Stefano Fogli, Sara Galimberti, Veronica Gori, Marzia Del Re, Romano Danesi
Summary: This review article explores the differences in potency, selectivity, pharmacokinetics, safety, and drug-drug interactions of clinically validated proteasome inhibitors, aiming to provide useful information for their clinical use in real life settings.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Wenhu Zhan, Hao Zhang, John Ginn, Annie Leung, Yi J. Liu, Mayako Michino, Akinori Toita, Rei Okamoto, Tzu-Tshin Wong, Toshihiro Imaeda, Ryoma Hara, Takafumi Yukawa, Sevil Chelebieva, Patrick K. Tumwebaze, Maria Jose Lafuente-Monasterio, Maria Santos Martinez-Martinez, Jeremie Vendome, Thijs Beuming, Kenjiro Sato, Kazuyoshi Aso, Philip J. Rosenthal, Roland A. Cooper, Peter T. Meinke, Carl F. Nathan, Laura A. Kirkman, Gang Lin
Summary: Studies have shown that Plasmodium falciparum proteasome inhibitors have the potential to treat, prevent, and block transmission of malaria. A noncovalent, macrocyclic peptide inhibitor with high species selectivity and improved pharmacokinetic properties has been developed, demonstrating specific inhibition of the Pf20S beta 5 subunit.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Pharmacology & Pharmacy
Long Meng, Jing Huang, Feng Qiu, Xuefeng Shan, Lin Chen, Shusen Sun, Yuwei Wang, Junqing Yang
Summary: The study identified an association between the combined use of proteasome inhibitors (PI) and factor Xa inhibitors (FXaI) leading to an increased reporting of peripheral neuropathy (PN) through analysis of FAERS data. Further preclinical and clinical studies are needed to elucidate this relationship.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Romina A. Guedes, Jorge H. Grilo, Andreia N. Carvalho, Pedro M. P. Fernandes, Ana S. Ressurreicao, Vanessa Brito, Adriana O. Santos, Samuel Silvestre, Eleonora Gallerani, Maria Joao Gama, Riccardo Gavioli, Jorge A. R. Salvador, Rita C. Guedes
Summary: The purpose of this study was to discover novel proteasome inhibitors with anticancer activity to overcome the limitations of existing inhibitors. A structure-based virtual screening protocol was developed using the human 20S proteasome structure, and 246 compounds were selected for in vitro evaluation. Compound 4 (JHG58) was shortlisted as the best hit compound based on its proteasome inhibitory activity and ability to induce cell death. Molecular docking studies revealed its interactions with key residues at the catalytic active site.
Review
Pharmacology & Pharmacy
Zsofia Varga-Medveczky, Dorottya Kocsis, Marton Bese Naszlady, Katalin Fonagy, Franciska Erdo
Summary: This article discusses the various technologies and devices used in testing drug delivery through the skin barrier, as well as the advancements in skin diffusion measurements and methodologies applied at Pazmany Peter Catholic University. Key achievements include validation of new skin-on-a-chip microfluidic devices for drug penetration studies and the finding that hydrophilic model drugs have lower penetration in aged skin.
Article
Chemistry, Medicinal
Gergely Takacs, David Havasi, Mark Sandor, Zsolt Dohanics, Gyorgy T. Balogh, Robert Kiss
Summary: In this study, a Do-It-Yourself (DIY) combinatorial chemistry library containing over 14 million almost completely novel products was presented. The library was built from 1000 low-cost building blocks and demonstrated its applicability in various drug discovery approaches. The internally built DIY chemical library was found to provide a viable alternative to external virtual catalogs by offering access to a large number of low-cost and quickly accessible potential chemical starting points for drug discovery.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Angelica Ferro, Dafni Graikioti, Emre Gezer, Constantinos M. M. Athanassopoulos, Muriel Cuendet
Summary: Although proteasome inhibitors have been used as the main treatment for multiple myeloma, patients often relapse and become resistant to drugs. Combining proteasome and histone deacetylase inhibitors has been found to be more effective, as it enhances anti-myeloma activity and improves patient outcomes. Hybrid molecules that combine the pharmacophores of entinostat and bortezomib have been synthesized and shown to have strong antiproliferative activity in multiple myeloma cells, including those resistant to bortezomib, as well as inhibiting histone deacetylase and proteasome activity.
Article
Pharmacology & Pharmacy
Gaojie Xu, Sheng Huang, Jian Peng, Xiaofang Gao, Minhui Li, Sisi Yu, Zuofeng Liu, Pengfan Qie, Yu Wang, Siqi Yu, Siyuan Liu, Hu Wen, Lijuan Su, Ping Li, Bin Guang, Renhan Dong, Jin Liu, Tai Yang
Summary: The study demonstrates the synergistic effect of lipid regulators with proteasome inhibitors in killing multiple myeloma cells. The novel derivative FCE shows significant synergy with ixazomib in vitro and in vivo. The abnormal lipid accumulation in multiple myeloma cells induced by proteasome inhibitors may be attributed to elevated SREBP1/2 expression induced by ATF4.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Oncology
Philip Weir, David Donaldson, Mary Frances McMullin, Lisa Crawford
Summary: Multiple myeloma is a common blood cancer that affects plasma cells in bone marrow. Despite improvements in treatment options, drug resistance remains a challenge. This review discusses the metabolic changes in multiple myeloma and the development of resistance to proteasome inhibitors, and explores potential therapeutic interventions.
Review
Chemistry, Multidisciplinary
Antonio Jose Guillot, Miquel Martinez-Navarrete, Teresa M. Garrigues, Ana Melero
Summary: Lipid vesicles offer cost-effective improvement in skin drug absorption when the production process is optimized. Designing the ideal vesicle is a significant challenge as their properties are interrelated. Size, deformability degree, and drug loading are the key features that determine transdermal drug absorption. Interest in this technology is growing exponentially, although commercialization has been limited by preservation and scalability issues, which can be overcome with freeze-drying and modern escalation methods. This predicts wider use of these technologies in the market and clinical practice.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Chemistry, Multidisciplinary
Sabrina R. Mackinnon, Gustavo A. Bezerra, Tobias Krojer, Tamas Szommer, Frank von Delft, Paul E. Brennan, Wyatt W. Yue
Summary: The study discovered six low-molecular-weight fragments that bind to different sites on the HAO1 structure, demonstrating their potential as inhibitors of HAO1.
FRONTIERS IN CHEMISTRY
(2022)
Article
Microbiology
Maria E. Cilento, Aaron B. Reeve, Eleftherios Michailidis, Tatiana Ilina, Eva Nagy, Hiroaki Mitsuya, Michael A. Parniak, Philip R. Tedbury, Stefan G. Sarafianos
Summary: The study demonstrates that EFdA exhibits exceptional potency against HIV-1, with M184V and A114S/M184V identified as key mutations contributing to EFdA resistance. These mutations show higher sensitivity to tenofovir and are suitable for use in treatment of naive, AZT, FTC/3TC, and tenofovir-treated patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Oncology
Yang Bai, Xing Su
Summary: Proteasome inhibitors (PIs) have been crucial therapies for myeloma patients, targeting the overstressed 26S proteasome involved in the disease pathogenesis. However, the major limitation in PI therapy lies in the acquisition of resistance, despite recent advancements in clinical antimyeloma treatment.
ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Instruments & Instrumentation
Sven Falke, Karsten Dierks, Clement Blanchet, Melissa Graewert, Florent Cipriani, Rob Meijers, Dmitri Svergun, Christian Betzel
JOURNAL OF SYNCHROTRON RADIATION
(2018)
Article
Chemistry, Multidisciplinary
Panagis Polykretis, Enrico Luchinat, Alessio Bonucci, Andrea Giachetti, Melissa A. Graewert, Dmitri I. Svergun, Lucia Banci
Article
Biochemistry & Molecular Biology
Norbert Nagel, Melissa A. Graewert, Mimi Gao, Winfried Heyse, Cy M. Jeffries, Dmitri Svergun, Harald Berchtold
BIOPHYSICAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Nikolina Trstenjak, Dalibor Milic, Melissa A. Graewert, Harald Rouha, Dmitri Svergun, Kristina Djinovic-Carugo, Eszter Nagy, Adriana Badarau
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Sara Sajko, Irina Grishkovskaya, Julius Kostan, Melissa Graewert, Kim Setiawan, Linda Truebestein, Korbinian Niedermueller, Charlotte Gehin, Antonio Sponga, Martin Puchinger, Anne-Claude Gavin, Thomas A. Leonard, Dimitri I. Svergun, Terry K. Smith, Brooke Morriswood, Kristina Djinovic-Carugo
Article
Biology
Alex Macpherson, Maisem Laabei, Zainab Ahdash, Melissa A. Graewert, James R. Birtley, Monika-Sarah E. D. Schulze, Susan Crennell, Sarah A. Robinson, Ben Holmes, Vladas Oleinikovas, Per H. Nilsson, James Snowden, Victoria Ellis, Tom Eirik Mollnes, Charlotte M. Deane, Dmitri Svergun, Alastair D. G. Lawson, Jean M. H. van den Elsen
Summary: This study investigates the binding of four knob domain peptides with complement C5 and reveals their effects on the target. The research identifies a new allosteric mechanism for inhibiting C5 and expands the therapeutic scope of C5. Additionally, it introduces knob domains as new low molecular weight antibody fragments with therapeutic potential.
Article
Biochemistry & Molecular Biology
Julius Kostan, Miha Pavsic, Vid Puz, Thomas C. Schwarz, Friedel Drepper, Sibylle Molt, Melissa Ann Graewert, Claudia Schreiner, Sara Sajko, Peter F. M. van der Ven, Adekunle Onipe, Dmitri Svergun, Bettina Warscheid, Robert Konrat, Dieter O. Fuerst, Brigita Lenarcic, Kristina Djinovic-Carugo
Summary: This study revealed the conformational ensembles of myotilin in solution and established a structural model of the F-actin:myotilin complex. The findings suggest a novel role of myotilin as a co-organizer of Z-disc assembly.
Article
Biochemistry & Molecular Biology
Andrea Bernardini, Mariangela Lorenzo, Antonio Chaves-Sanjuan, Paolo Swuec, Matteo Pigni, Dana Saad, Petr V. Konarev, Melissa Ann Graewert, Erica Valentini, Dmitri I. Svergun, Marco Nardini, Roberto Mantovani, Nerina Gnesutta
Summary: NF-Y cooperates with USF1 in DNA binding and jointly activates target promoters. Certain unstructured domains adapt to small variations in stereo-alignments of TF sites.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Petr Konarev, Melissa A. Graewert, Cy M. Jeffries, Masakazu Fukuda, Taisiia A. Cheremnykh, Vladimir V. Volkov, Dmitri Svergun
Summary: SAXS is commonly used for structural analysis of biological macromolecules in solution, and combining SAXS with chromatography setups has become popular in research. The computer program EFAMIX, based on evolving factor analysis (EFA), efficiently restores scattering and concentration profiles of components from mixed SAXS data, proving useful for interpretation and analysis of fractions in the sample.
Article
Multidisciplinary Sciences
Ivan Corbeski, Xiaohu Guo, Bruna Eckhardt, Domenico Fasci, Wouter Wiegant, Melissa A. Graewert, Kees Vreeken, Hans Wienk, Dmitri Svergun, Albert J. R. Heck, Haico van Attikum, Rolf Boelens, Titia K. Sixma, Francesca Mattiroli, Hugo van Ingen
Summary: Nucleosome assembly requires specific histone chaperones, but this study found that the acidic domain of DNA repair factor APLF can directly assemble the histone octamer and deposit it on DNA to form nucleosomes, which may be a mechanism for histone chaperone function at sites where chromatin is temporarily disrupted.
Article
Biochemical Research Methods
Jill Trewhella, Patrice Vachette, Jan Bierma, Clement Blanchet, Emre Brookes, Srinivas Chakravarthy, Leonie Chatzimagas, Thomas E. Cleveland, Nathan Cowieson, Ben Crossett, Anthony P. Duff, Daniel Franke, Frank Gabel, Richard E. Gillilan, Melissa Graewert, Alexander Grishaev, J. Mitchell Guss, Michal Hammel, Jesse Hopkins, Qingqui Huang, Jochen S. Hub, Greg L. Hura, Thomas C. Irving, Cy Michael Jeffries, Cheol Jeong, Nigel Kirby, Susan Krueger, Anne Martel, Tsutomu Matsui, Na Li, Javier Perezt, Lionel Porcar, Thierry Prange, Ivan Rajkovic, Mattia Rocco, Daniel J. Rosenberg, Timothy M. Ryan, Soenke Seifert, Hiroshi Sekiguchi, Dmitri Svergun, Susana Teixeira, Aurelien Thureaut, Thomas M. Weiss, Andrew E. Whitten, Kathleen Wood, Xiaobing Zuo
Summary: By collecting SAXS and SANS measurements, consensus scattering profiles for proteins were obtained, which were consistent with theoretical predictions. Optimization of sample purification methods and measurement conditions can improve the quality and precision of the data.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Rita Fernandes, Anna Ostendorp, Steffen Ostendorp, Judith Mehrmann, Sven Falke, Melissa Ann Graewert, Magdalena Weingartner, Julia Kehr, Stefan Hoth
Summary: Ribosome biogenesis is a vital process in eukaryotic cells that involves numerous ribosome biogenesis factors (RBFs), which are essential for assembling mature ribosomes consisting of proteins and rRNAs. While rRNA processing has been extensively studied in yeast and mammals, there is still limited knowledge about this process in plants. This study focused on a plant RBF called NUCLEOLAR RNA CHAPERONE-LIKE 1 (NURC1) from Arabidopsis thaliana, which was found to be localized in the nucleolus of plant cell nuclei.
SCIENTIFIC REPORTS
(2023)
Article
Biochemical Research Methods
Masakazu Fukuda, Melissa A. Graewert, Cy M. Jeffries, Dmitri I. Svergun, Tadao Yamazaki, Akiko Koga, Yuji Yamanaka
Summary: This study investigates the acidic variants of therapeutic monoclonal antibodies (mAbs) using a refolding approach. The results showed that these acidic variants are conformational variants with minor and localized conformational changes.
ANALYTICAL BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Tania F. Custodio, Hrishikesh Das, Daniel J. Sheward, Leo Hanke, Samuel Pazicky, Joanna Pieprzyk, Michele Sorgenfrei, Martin A. Schroer, Andrey Yu. Gruzinov, Cy M. Jeffries, Melissa A. Graewert, Dmitri I. Svergun, Nikolay Dobrev, Kim Remans, Markus A. Seeger, Gerald M. McInerney, Ben Murrell, B. Martin Haellberg, Christian Loew
NATURE COMMUNICATIONS
(2020)
Article
Crystallography
Melissa A. Graewert, Stefano Da Vela, Tobias W. Graewert, Dmitry S. Molodenskiy, Clement E. Blanchet, Dmitri I. Svergun, Cy M. Jeffries
Review
Chemistry, Multidisciplinary
Dan He, Yawen Li, Fuwen Zhao, Yuze Lin
Summary: High trap density in organic solar cells leads to localized charge carriers and reduced carrier lifetime, limiting device efficiency. This feature article summarizes the recent advances of trap suppression by material design and device engineering.
CHEMICAL COMMUNICATIONS
(2024)
Review
Chemistry, Multidisciplinary
Olivier Monfort, Arshitha Madhusudhan, Martin Motola
Summary: This article presents the advantages of coupling photocatalysis and Fenton-based processes for environmental remediation and discusses their synergy. It critically examines the simultaneous triggering of these two processes and provides insights into research approaches. The study aims to enhance understanding of this complex process and highlight the potential integration of new catalysts in current wastewater treatment technology.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Manideepa Dhar, Chittaranjan Mishra, Avijit Das, Uttam Manna
Summary: An approach of 'polymerization of monomers in its aggregated form' has been introduced to tailor the water wettability of fibrous and porous substrates, achieving hydrophobicity to superhydrophobicity transition, as well as patterned wettability. This facile chemical method provides a durable coating with adjustable and patterned wettability for various potential applications.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Saswat Ranjan Bhoi, Chhanda Debnath, Shikha Gandhi
Summary: In this article, a novel catalytic reaction using Pd(0) and Bronsted acid is reported for the synthesis of biologically important imidazolidinone-fused N-heterocycles through redox-neutral intramolecular N-allylation of indoles and pyrroles with alkynes. This atom-economical method is applicable to a wide range of substrates and eliminates the need for leaving groups or oxidizing agents commonly used in traditional allylation reactions.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Longkun Chen, Mingshuai Zhang, Meichen Liu, Zhuoyuan Liu, Yuetong Qiu, Zhilai Zhang, Fuchao Yu, Jiuzhong Huang
Summary: In this study, an efficient Rh(III)-catalyzed selective mono- and dual-C-H bond functionalization/cyclization with iodonium ylide as the sole coupling partner was demonstrated. Fused benzodiazepine skeletons were obtained in excellent yields, providing an improved approach to dual C-H unsymmetrical functionalization.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Alice Kennett, Sven Epple, Gabriella van der Valk, Irene Georgiou, Evelyne Gout, Romain R. Vives, Angela J. Russell
Summary: This study presents the design and synthesis of sulfated disaccharide inhibitors based on IdoA(2S)-GlcNS(6S), which showed potent inhibition of Sulf-2. The results suggest that IdoA(2S)-GlcNS(6S) is the shortest fragment size required for effective inhibition of Sulfs, and a trisulfated disaccharide is identified as the minimal fragment size of heparan sulfate for effective endosulfatase inhibition.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Mauro Garbini, Andrea Brunetti, Riccardo Pedrazzani, Magda Monari, Massimo Marcaccio, Giulio Bertuzzi, Marco Bandini
Summary: The self-adaptability of galvanostatic electrolysis was found to be helpful in a multistage chemo- and diastereoselective electrochemically promoted cyclodimerization of chalcones. Through a series of reductive events, densely functionalized cyclopentanes with five contiguous stereocenters were obtained (25 examples, yields up to 95%, dr values up to >20:1). Further experimental and electrochemical investigations indicated the crucial role of dynamic kinetic resolution of the aldol intermediate in the reaction mechanism.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Dhananjay S. Nipate, Neha Meena, Prakash N. Swami, Krishnan Rangan, Anil Kumar
Summary: In this study, the synthesis of functionalized benzo[a]phenazines and indazolo[2,3-a]quinolines was achieved through Rh(III)-catalyzed oxidative annulation of 2-arylquinoxalines and 2-aryl-2H-indazoles with allyl alcohols. The method showed a wide substrate scope, excellent functional group tolerance, good to high yields of annulated products, and the capability for scaled-up synthesis. A tentative mechanism of the annulation reaction was proposed based on a preliminary mechanistic investigation.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Ruonan Zhang, Abudukadi Tudi, Xia Yang, Xuping Wang, Zhihua Yang, Shujuan Han, Shilie Pan
Summary: A new lead tellurium borate material with a unique fundamental building block [B4O10] was synthesized and found to exhibit high birefringence. The structure-property relationship was discussed using first-principles calculations.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Amresh Kumar Singh, Baishali Thakurta, Anupam Giri, Monalisa Pal
Summary: This study introduces three key concepts for the quick synthesis of large-scale high-quality 2D materials films and their utilization in device fabrication.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Reina Hagiwara, Shun Nishimura, Kosuke Okeyoshi
Summary: A copolymer-conjugated nanocatalytic system has been developed to improve electron transfer and enhance photoinduced H2 generation.
CHEMICAL COMMUNICATIONS
(2024)