Article
Chemistry, Multidisciplinary
Jehad Almaliti, Pavla Fajtova, Jaeson Calla, Gregory M. LaMonte, Mudong Feng, Frances Rocamora, Sabine Ottilie, Evgenia Glukhov, Evzen Boura, Raymond T. Suhandynata, Jeremiah D. Momper, Michael K. Gilson, Elizabeth A. Winzeler, William H. Gerwick, Anthony J. O'Donoghue
Summary: We have developed epoxyketone-based proteasome inhibitors that exhibit potent activity against blood-stage Plasmodium falciparum with low cytotoxicity to human cells. These inhibitors demonstrated high selectivity for the erythrocytic-stage P. falciparum over human cells, attributed to the parasite proteasome's accommodation of a D-amino acid and preference for a difluorobenzyl group. The best compound has strong inhibitory activity against the beta 5 subunit of P. falciparum proteasome and shows promising efficacy in reducing parasitemia and prolonging survival in a mouse infection model. These compounds serve as promising starting points for the development of orally bioavailable anti-malarial drugs.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Jehad Almaliti, Muhammed Alzweiri, Momen Alhindy, Tamam Al-Helo, Ibrahim Daoud, Raghad Deknash, C. Benjamin Naman, Bashaer Abu-Irmaileh, Yasser Bustanji, Islam Hamad
Summary: This study investigated a series of epoxyketone peptide derivatives and found that many of these derivatives showed potent anti-lipase activity, regardless of the configuration of the epoxide in the epoxyketone moiety. This is the first example of using epoxyketone peptides as novel lipase inhibitors.
Article
Microbiology
Bruna Domingues Vieira, Henrique Niero, Rafael de Felicio, Luiz Fernando Giolo Alves, Cristina Freitas Bazzano, Renata Sigrist, Luciana Costa Furtado, Gabriela Felix Persinoti, Leticia Veras Costa-Lotufo, Daniela Barretto Barbosa Trivella
Summary: Streptomyces sp. BRA-346 is a type of actinobacteria isolated from the Brazilian endemic tunicate Euherdmania sp. Research has shown that this strain produces epoxyketone peptides, which inhibit proteasome activity and exhibit high cytotoxicity to glioma cells. However, the low yields and poor reproducibility of epoxyketone peptides production by BRA-346 under laboratory conditions have hindered further studies. By evaluating different cultivation methods, culture media, and chemical elicitors, as well as sequencing the BRA-346 genome and using metabolomics, researchers have demonstrated the potential of BRA-346 to produce epoxyketone peptides and shed light on its regulatory mechanisms.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Plant Sciences
Ya-Jun Yang, Ke Wang, Ying Yang, Fang-Fang Lai, Xiao-Guang Chen, Zhi-Yan Xiao
Summary: The designed series of dipeptide inhibitors show significant inhibitory activities against the chymotrypsin-like activity of human 20S proteasome, suggesting their potential as effective inhibitors.
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Lisa Marinelli, Michele Ciulla, Jeffrey A. S. Ritsema, Cornelus F. van Nostrum, Ivana Cacciatore, Marilisa Pia Dimmito, Ferdinando Palmerio, Giustino Orlando, Iole Robuffo, Rossella Grande, Valentina Puca, Antonio Di Stefano
Summary: The aim of this study was to encapsulate antimicrobial peptide FS10 in PEG-PLGA nanoparticles to overcome the limitations of hydrophilic drugs. The pH value and polymeric composition were found to be influential parameters for encapsulation efficiency. FS10-PEG-PLGA nanoparticles obtained under optimized parameters showed good size and surface potential, with sustained drug release. Antimicrobial assay demonstrated that the FS10-loaded nanoparticles had a lower minimum inhibitory concentration against S. aureus.
Article
Immunology
Sumin Kim, Seo Hyeong Park, Won Hoon Choi, Min Jae Lee
Summary: This paper describes a protocol for measuring the activity of immunoproteasomes using commercially available fluorogenic peptide substrates. The results suggest that the most accurate assessment of immunoproteasome activity can be achieved by combining a specific substrate and an immunoproteasome inhibitor. This simple and reliable method may contribute to future studies on the role of immunoproteasomes in viral infection, inflammation, and tumorigenesis.
Article
Chemistry, Medicinal
Bin Zhang, Zhikun Liu, Shengjin Xia, Qingqing Liu, Shaohua Gou
Summary: Multi-target, especially dual-target, drug design is a popular research field in cancer treatment. This study developed quinazoline derivatives as dual EGFR/CAIX inhibitors, with compound 8v showing potent anticancer activity against mutant-type lung cancer cells, especially under hypoxic conditions. Mechanism studies revealed that 8v exhibited strong inhibitory effects on both EGFR(T790M) and CAIX enzymes, making it a promising candidate for further research in cancer therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Sophia D. Staerz, Corey L. Jones, Jetze J. Tepe
Summary: Neurodegenerative diseases are characterized by the oligomerization and aggregation of specific intrinsically disordered proteins, and enhancing 20S proteasome-mediated proteolysis could be a promising therapeutic approach.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Jinhai Wang, Ying Fang, R. Andrea Fan, Christopher J. Kirk
Summary: The proteasome plays a crucial role in tumor and immune cell biology, serving as a therapeutic target for drug development. Various inhibitors have been approved for the treatment of multiple myeloma, with ongoing development of selective immunoproteasome inhibitors for autoimmune diseases. Researchers compare the pharmacokinetics, pharmacodynamics, and metabolism of these compounds, highlighting the distinct metabolism pathway of peptide epoxyketones as a favorable property for chronic conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Materials Science, Multidisciplinary
Lang Long, Zhiqiang Yang, Kaicheng Zeng, Zhishen Huang, Xuedan Hou, Hongxia Zhao
Summary: In this study, a water-soluble chondroitin sulfate-curcumin conjugate (CS-Cur) was synthesized to improve the solubility of curcumin in pharmaceutical applications. The CS-Cur was characterized using NMR, FTIR, and TEM. Cell experiments showed that CS-Cur had a significant inhibitory effect on tumor cells.
Article
Chemistry, Multidisciplinary
Yoshihiro Ishimaru, Tomohide Moteki, Miho Suzuki, Tetsuo Koyama, Takahiko Matsushita, Ken Hatano, Koji Matsuoka
Summary: A water-soluble glycopolymer bearing porphyrin moieties was synthesized by radical polymerization, and its potential as an anti-cancer agent was confirmed.
Article
Biochemistry & Molecular Biology
Xiaoyi Zhang, Tong Zhao, Minghao Sun, Pei Li, Mengzhen Lai, Lingfeng Xie, Jiaying Chen, Jian Ding, Hua Xie, Jinpei Zhou, Huibin Zhang
Summary: Several small-molecule covalent inhibitors of KRASG12C have shown promising breakthroughs in treating KRAS mutant cancer. However, adaptive resistance may limit the clinical application of these inhibitors. The emerging PROTAC strategy offers complementary advantages and improves anti-tumor efficacy. Through protein degradation and anti-proliferative activities, novel KRASG12C-PROTACs have been demonstrated to effectively bind and degrade KRASG12C, surpassing the potency of AMG-510. Mechanistic studies indicate degradation effects through the ubiquitin-proteasome pathway. These findings support the use of PROTACs for degrading the oncogene KRASG12C and provide insights for optimizing the structure of KRASG12C-PROTACs.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Sirin Uysal, Zeynep Soyer, Merve Saylam, Ayse H. Tarikogullari, Sinem Yilmaz, Petek Ballar Kirmizibayrak
Summary: A series of novel 4-aminobenzensulfonamide/carboxamide derivatives bearing naphthoquinone pharmacophore were synthesized and evaluated for their proteasome inhibitory and anti-proliferative activities against human breast cancer cell line (MCF-7). The results showed that some compounds exhibited significant inhibitory effects on proteasome activity, with compounds 13 and 28 showing the highest anti-proliferative activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Yiqing Yang, Tongke Tang, Xiaolu Li, Thomas Michel, Liqin Ling, Zhenghui Huang, Maruthi Mulaka, Yue Wu, Hongying Gao, Liguo Wang, Jing Zhou, Brigitte Meunier, Hangjun Ke, Lubin Jiang, Yu Rao
Summary: This study identified a novel multi-targeting antimalarial molecule RYL-581 through structure-based drug design, which binds to multiple protein binding sites of Plasmodium falciparum. The compound effectively kills various drug-resistant strains in vitro and exhibits good solubility as well as in vivo activity, suggesting its potential in future drug discovery projects targeting membrane-associated targets.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Chemistry, Medicinal
Markus Klein, Michael Busch, Manja Friese-Hamim, Stefano Crosignani, Thomas Fuchss, Djordje Musil, Felix Rohdich, Michael P. Sanderson, Jeyaprakashnarayanan Seenisamy, Gina Walter-Bausch, Ugo Zanelli, Philip Hewitt, Christina Esdar, Oliver Schadt
Summary: Proteasomes are essential components of the ubiquitin-dependent protein degradation pathway, with LMP7 being a subunit of the immunoproteasome. Current pan-proteasome inhibitors nonselectively target LMP7 and other subunits, limiting their therapeutic applicability. Novel amido boronic acids were discovered to selectively inhibit LMP7, leading to the identification of the highly potent and orally available inhibitor M3258, which showed strong antitumor activity in MM models.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Zhuangzhuang Zhang, Qiao Hu, Jiaying Liao, Yifan Xu, Ruiqi Tian, Yichen Du, Jian Shen, Xiaosi Zhou
Summary: A self-templating strategy was used to prepare homogeneous P2-K0.6CoO2 (KCO) microcubes, which showed improved electrochemical properties for potassium storage due to the reduced interface between the electrolyte and the active material.
Article
Chemistry, Organic
Bo Dong, Yifeng Chen, Shubing Xie, Jieying Zhang, Jian Shen, Lan-Gui Xie
Summary: Oxidative cross-coupling of two thiols is a direct and desirable method for synthesizing unsymmetrical disulfides. However, the formation of symmetrical by-products is a major issue. This study presents a method where the homo-coupling of thiols is effectively inhibited by sequential addition of the thiols, utilizing the rapid oxidation of thiols by bromodimethylsulfonium bromide.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Biophysics
Shuqing Xiang, Mingqian Wang, Li Li, Jian Shen
Summary: A photothermal/photodynamic/NO synergistic antibacterial nanoplatform was proposed by loading L-arginine (LA) on mesoporous TiO2 and encapsulating it with polydopamine. The obtained TiO2_x-LA@PDA nanocomposite exhibited excellent antibacterial effects against various bacteria, along with the ability to generate nitric oxide (NO) under near-infrared (NIR) light irradiation. The developed nanoplatform can be further explored in the biomedical field of photothermal activation of multimodal combined antibacterial therapy.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Yu Sun, Pengcheng Liu, Jie Zhang, Lijuan Wang, Yushuang Shang, Jian Shen, Jiang Yuan
Summary: In this study, a protein-polymer conjugate was synthesized, combining the chemical properties of a synthetic polymer chain with the biological properties of a protein. The conjugate self-assembled to form micelles with low critical micelle concentration and good blood compatibility. The drug-loaded micelles exhibited triple responsiveness to pH, glutathione, and trypsin under tumor microenvironments, showing high toxicity against A549 cells while low toxicity on normal cells and prolonged blood circulation.
Article
Chemistry, Multidisciplinary
Wan Peng, Cheng Liu, Youjin Lai, Yanting Wang, Pingsheng Liu, Jian Shen
Summary: Most bioadhesives are ineffective on bleeding tissues and postoperative adhesion is a common issue. A three-layer biodegradable Janus tissue patch (J-TP) is developed to efficiently close bleeding wounds, promote clotting, and prevent tissue adhesion. The J-TP's adhesive hydrogel bottom layer forms strong adhesion to bleeding tissues through chemical bonding, while the middle layer improves tensile strength and the top layer prevents postoperative adhesion and inflammation. This J-TP shows promise in the clinical treatment of injured bleeding tissues with inhibited adhesion.
Article
Engineering, Biomedical
Peiming Liu, Jin Sun, Wan Peng, Yahui Gu, Xiaoxue Ji, Zhi Su, Pingsheng Liu, Jian Shen
Summary: Good's buffers have been widely used in cell/organ culture as biocompatible pH stabilizers. However, the emergence of adverse effects such as cellular uptake, autophagic activation, and cytotoxicity under light exposure raises concerns over its biocompatibility. Riboflavin in the cell culture medium produces reactive oxygen species (ROS) under light exposure, causing severe toxicity and disruption of normal cell functions. Zwitterionic betaines have been identified as a new generation of biocompatible pH buffers that do not exhibit these adverse effects.
BIOACTIVE MATERIALS
(2023)
Article
Nanoscience & Nanotechnology
Cheng Liu, Huimin Gao, Gaoqi Sun, Xuefeng Jiang, Saijie Song, Jun Zhang, Jian Shen
Summary: In this study, a multifunctional decellularized scaffolds (DCS)-based vascular patch was designed for porcine vascular repair. By coating ammonium phosphate zwitter-ion (APZI) and poly(vinyl alcohol) (PVA) hydrogel on the surface of DCS, the mechanical properties and biocompatibility of the artificial vascular patch were improved. The artificial vascular patch was further decorated with a heparin (Hep)-loaded metal-organic framework (MOF) to inhibit blood coagulation and promote vascular endothelialization. The results showed that the obtained artificial vascular patch had suitable mechanical properties, good biocompatibility, and blood compatibility, making it an excellent vascular replacement material.
ACS APPLIED BIO MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Yushuang Shang, Penghui Wang, Xiuzhen Wan, Lijuan Wang, Xu Liu, Jiang Yuan, Bo Chi, Jian Shen
Summary: Multifunctional hydrogel dressings with chlorhexidine(CHX) loaded double network hydrogels showed cytocompatibility, antioxidant capability, and enhanced antibacterial activity. The hydrogels exhibited acid, glutathione(GSH), and trypsin triple-responsive release behaviors, accelerating CHX release under wound microenvironments. The freeze-drying hydrogels could be ground into powders and sprinkled on irregular wounds to reform hydrogel in situ, which were more convenient for sterilization, formulation, and storage. The xerogel powder dressing significantly promoted collagen deposition and reduced inflammation in vivo, accelerating wound closure and regeneration.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Energy & Fuels
Qihui He, Xin Wang, Dongqing Dai, Yahui Feng, Renfu Xu, Jiandang Yan, Pengfei Wang, Jian Shen, Baixing Hu
Summary: In this study, the structures and properties of degradation products of polystyrene (PS) waste were characterized, and the optimal degradation conditions were investigated using various analytical techniques. It was found that using 1.0 wt% K2S2O8 as an assistant at 300°C for 24 hours was suitable for degrading PS waste. The degraded PS was then prepared into sodium polystyrene sulfonate (PSS), which showed excellent performance as a dispersant for coal-water slurry (CWS) when it had a sulfonation degree of more than 75% and a number average molecular weight (Mn) of about 9000.
INTERNATIONAL JOURNAL OF COAL PREPARATION AND UTILIZATION
(2023)
Article
Chemistry, Analytical
Qian Chen, Wenyan Guo, Dan Fang, Ting Li, Lin Chen, Chun Mao, Mimi Wan, Jian Shen
Summary: Efficient capture and detection of circulating tumor cells (CTCs) using Mg-Based micromotors was achieved, which is crucial for early cancer detection.
SENSORS AND ACTUATORS B-CHEMICAL
(2023)
Article
Chemistry, Multidisciplinary
Juyang Zhang, Mengdi Lv, Xinye Wang, Fan Wu, Cheng Yao, Jian Shen, Ninglin Zhou, Baohong Sun
Summary: Nanozyme-driven catalytic antibacterial therapy using biomimetic nanoenzymes can effectively target inflamed areas and eliminate bacterial biofilms. This approach overcomes limitations of current biofilm wound treatments and offers potential for improved outcomes.
Article
Chemistry, Multidisciplinary
Lei He, Yongze Liu, Panpan Song, Fuqi Feng, Genyuan Li, Yuanyuan Ma, Juqing Cui, Xiaofeng Ma, Jian Shen, Jun Zhang
Summary: A highly efficient photothermal and flexible wood-based hydrogel has been successfully synthesized, which promotes the recovery of infected wounds and is nontoxic, renewable, and biodegradable. It exhibits good photothermal conversion efficiency and long-lasting antibacterial effects, making it a potential biomaterial for the treatment of infected skin wounds.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Review
Materials Science, Biomaterials
Nian Liu, Xiangyu Xiao, Ziqiang Zhang, Chun Mao, Mimi Wan, Jian Shen
Summary: Cancer vaccines are a promising therapeutic strategy in clinical oncology, stimulating antitumor immunity to fight against cancer. However, there are several challenges that hinder their broad clinical translation.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Article
Nanoscience & Nanotechnology
Cheng Liu, Huimin Gao, Gaoqi Sun, Xuefeng Jiang, Saijie Song, Jun Zhang, Jian Shen
Summary: In this study, a multifunctional decellularized scaffolds (DCS)-based vascular patch with improved mechanical properties and biocompatibility was designed. The surface of the patch was coated with ammonium phosphate zwitter-ion (APZI) and poly(vinyl alcohol) (PVA) hydrogel, followed by the decoration of a heparin (Hep)-loaded metal-organic framework (MOF) to inhibit blood coagulation and promote vascular endothelialization. The obtained artificial vascular patch showed suitable mechanical properties, good biocompatibility, and blood compatibility. It also demonstrated enhanced proliferation and adhesion of endothelial progenitor cells (EPCs). The results from imaging techniques confirmed the patency of the implanted artificial vascular patch.
ACS APPLIED BIO MATERIALS
(2023)
Article
Chemistry, Physical
Gaoqi Sun, Xuefeng Jiang, Cheng Liu, Saijie Song, Jun Zhang, Jian Shen
Summary: The abuse of antibiotics leads to bacterial resistance, and it is important to develop new strategies for efficient antibacterial and wound healing. This study introduces a FeS@LAB-35@Ti3C2 nanozyme that integrates photothermal and chemodynamic therapy for bacterial inhibition and wound healing.