Article
Chemistry, Medicinal
Siqi Zhang, Xiaolei Meng, Sai Zhang, Baohu Li, Wencong Jin, Chengwei Zhang, Zhaojuan Liu, Xiaolin Hu, Ling Ge, Zhonghao Yu, Zhuoyue Li, Shumin Ma, Xiao Wang, Liming Li, Chong Qin
Summary: Androgen deprivation in castration-resistant prostate cancer can have adverse effects, but tumor-specific suppression of androgen receptor signaling may reduce side effects. This study presents a new class of small molecular conjugates that can target prostate cancer cells and suppress AR function by binding to Hsp90. These conjugates showed improved tumor-targeting ability and enhanced potency against Enzalutamide-resistant cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Xiaohui Wang, Jun Zhang, Zhijian Han, Liheng Ma, Yumin Li
Summary: A novel probe, F-18-NOTA-Dimer-San A, was developed for PET imaging of Hsp90 expression in pancreatic cancer and has the potential to discriminate pancreatic cancer from inflammatory mass.
Article
Cell Biology
Sandra Backes, Yury S. Bykov, Tamara Flohr, Markus Raeschle, Jialin Zhou, Svenja Lenhard, Lena Kraemer, Timo Muehlhaus, Chen Bibi, Cosimo Jann, Justin D. Smith, Lars M. Steinmetz, Doron Rapaport, Zuzana Storchova, Maya Schuldiner, Felix Boos, Johannes M. Herrmann
Summary: Tom70 protein functions at the interface of cytosol and mitochondria, recruiting cytosolic chaperones to the outer mitochondrial membrane to reduce proteotoxicity of mitochondrial precursor proteins.
Article
Chemistry, Organic
Abha Dangi, Bharat Pande, Sonia Agrawal, Dhiman Sarkar, Koteswara Rao Vamkudoth, Udaya Kiran Marelli
Summary: The first total synthesis of icosalide A, an antibacterial depsipeptide containing two lipophilic beta-hydroxy acids, was achieved using Fmoc solid-phase peptide synthesis and solution-phase synthesis. The absolute stereochemistry of icosalide A was determined by synthesizing reported structures and relevant diastereomers of icosalides and comparing their NMR data. Icosalide A exhibited a well-folded structure with cross-strand hydrogen bonds, and its analogues displayed antibacterial activity against Bacillus thuringiensis and Paenibacillus dendritiformis, as well as inhibitory effects on Mycobacterium tuberculosis and cancer cell lines HeLa and ThP1.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Marina Serna, Ana Gonzalez-Corpas, Sofia Cabezudo, Andres Lopez-Perrote, Gianluca Degliesposti, Eduardo Zarzuela, J. Mark Skehel, Javier Munoz, Oscar Llorca
Summary: This study reveals the role of ZNHIT2 in the regulation of R2TP chaperone during the biogenesis of PRPF8. ZNHIT2 forms a complex with R2TP and alters the conformation and nucleotide state of RUVBL1-RUVBL2, affecting its ATPase activity. PRPF8 interacts directly with R2TP and this complex can incorporate ZNHIT2 and other proteins involved in the biogenesis of PRPF8.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Analytical
Helisa H. Wippel, Juan D. Chavez, Andrew D. Keller, James E. Bruce
Summary: The XL-MS technique provides insight into protein conformations and interactions within their cellular environment, while the iqPIR strategy allows for comparative interactome studies using isotope encoded chemical cross-linkers. Multiplexed iqPIR enables quantitative interactome analysis of up to six biological samples in a single LC-MS acquisition, revealing specific protein conformational and interaction changes in response to different inhibitors.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Quan Zheng, Wen Zhang, Guo-Wu Rao
Summary: This article reviews the current research status of protein methyltransferase SMYD2 and the development of inhibitors. It evaluates the challenges in this field and provides insights into future directions.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Siddhi Omkar, Ainella Rysbayeva, Andrew W. Truman
Summary: The interactions between molecular chaperones and their clients can be influenced by post-translational modifications (PTMs) on chaperones, known as the 'chaperone code'. However, it is still not well understood how PTMs on client proteins may affect chaperone-client interactions. In this forum, we explore the potential of a 'client code' that may play a role in these interactions.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Chuan-jing Cheng, Kai-xin Liu, Man Zhang, Fu-kui Shen, Li-li Ye, Wen-bo Wu, Xiao-tao Hou, Er-wei Hao, Yuan-yuan Hou, Gang Bai
Summary: This study identified a novel natural inhibitor of HSP90, okicamelliaside (OCS), which selectively inhibits the formation of the HSP90-CDC37 protein complex and disrupts protein-protein interactions of HSP90-CDC37 to exert anti-tumor effects.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Chemistry, Multidisciplinary
Jesi R. Maguire, Conor J. Mccluskey, Kristina M. Holsgrove, Ahmet Suna, Amit Kumar, Raymond G. P. Mcquaid, J. Marty Gregg
Summary: We have used high-voltage Kelvin probe force microscopy to map the electrical potential distribution along curved current-carrying conducting domain walls in ferroelectric lithium niobate thin films. We found that the potential profiles and electric fields can be explained by variations in wall resistivity alone, without invoking additional physical phenomena. This is important for domain-wall nanoelectronics.
Article
Biochemistry & Molecular Biology
Alexandra D. Gurzau, Christopher R. Horne, Yee-Foong Mok, Megan Iminitoff, Tracy A. Willson, Samuel N. Young, Marnie E. Blewitt, James M. Murphy
Summary: SMCHD1 is an epigenetic regulator that mediates gene expression silencing, and dimerization of its N-terminal ATPase and C-terminal SMC hinge domains plays a crucial role in its function. The targeted deletion of the N-terminal UBL domain disrupts the localization of SMCHD1 to chromatin in cells, indicating its importance for chromatin interaction.
BIOCHEMICAL JOURNAL
(2021)
Article
Physics, Applied
Cheng Dai, Zijian Hong, Sujit Das, Yun-Long Tang, Lane W. Martin, Ramamoorthy Ramesh, Long-Qing Chen
Summary: The PTO/STO superlattice system has shown interesting topological phases besides normal ferroelectric domain states. This study focuses on studying the strain effect on the topological phase transitions and ferroelectric domain structures. The results provide guidance on manipulating polar structures in PTO/STO superlattices via strain engineering.
APPLIED PHYSICS LETTERS
(2023)
Review
Biochemistry & Molecular Biology
Samarpan Maiti, Didier Picard
Summary: The heat shock protein 90 (Hsp90) is a crucial molecular chaperone and regulator of protein stability in both normal and stressful conditions. In mammals, there are two cytosolic isoforms of Hsp90, Hsp90 alpha and Hsp90 beta, which have overlapping functions and interact with a majority of the proteome. Recent studies suggest that there may be differences in the specific functions of these isoforms, particularly in relation to certain tissues or cell types. Understanding the isoform-specific functions is important for designing therapeutic strategies.
Article
Biochemistry & Molecular Biology
Sarka Tumova, Marek Jindra
Summary: Juvenile hormone (JH) signalling plays a critical role in regulating insect development, but the molecular mechanisms are not well understood. This study investigated the dynamic aspect of JH signalling and revealed the rapid assembly and dissociation of JH receptor heterodimer from bHLH-PAS proteins upon JH binding. The study also demonstrated the regulatory role of the chaperone Hsp90/83 in the JH receptor complex formation.
Article
Biochemistry & Molecular Biology
Sunisa Yoodee, Paleerath Peerapen, Sirikanya Plumworasawat, Visith Thongboonkerd
Summary: This study found that heat-shock protein 90 (HSP90) and its four functional domains play important roles in the formation of kidney stones, promoting the crystallization, growth, aggregation, adhesion onto renal cells, and invasion through the extracellular matrix (ECM) of calcium oxalate monohydrate (COM) crystals.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)