Article
Chemistry, Multidisciplinary
Kedar N. Baryal, Sherif Ramadan, Guowei Su, Changxin Huo, Yuetao Zhao, Jian Liu, Linda C. Hsieh-Wilson, Xuefei Huang
Summary: A divergent approach was used to synthesize a library of HS tetrasaccharides that covered all possible sulfation structures. This library helped identify the structural requirements for HS sequences to bind to fibroblast growth factor-2 and showed weak affinity for platelet factor-4. This could lead to the development of new HS-based therapeutics without the adverse effect of heparin-induced thrombocytopenia.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Imlirenla Pongener, Conor O'Shea, Hannah Wootton, Michael Watkinson, Gavin J. Miller
Summary: This review focuses on the chemical approaches and methodology improvements for the synthesis of heparin and heparan sulfate since 2015, including advances in accessing the pentasaccharide anticoagulant and targets for heparan sulfate synthesis. It also discusses key building block synthesis, oligosaccharide construction, chemical sulfation techniques, and technological improvements to traditional solution-phase synthesis approaches.
Article
Biochemistry & Molecular Biology
Maurice Horton, Guowei Su, Lin Yi, Zhangjie Wang, Yongmei Xu, Vijayakanth Pagadala, Fuming Zhang, David A. Zaharoff, Ken Pearce, Robert J. Linhardt, Jian Liu
Summary: This study characterized HS interactions using a microarray of chemoenzymatically synthesized HS structures, highlighting the crucial role of specific sulfation patterns in protein binding. Screening and determining binding affinities of 95 different HS structures were consistent with previous studies. This technique is ideal for rapid expansion and will be pivotal for high-throughput characterization of biologically important structure/function relationships.
Review
Cell Biology
Jian Liu, Lars C. Pedersen
Summary: This article summarizes the recent progress in substrate specificity studies of different 3-O-sulfotransferase isoforms and introduces a newly developed method for analyzing the level of 3-O-sulfated heparan sulfate using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Kuei-Yao Tseng, Zheng-Hao Tzeng, Ting-Jen Rachel Cheng, Pi-Hui Liang, Shang-Cheng Hung
Summary: Researchers identified the minimal substrate size for Sulf-1 and designed and synthesized two Sulf-1 inhibitors with low IC50 values.
FRONTIERS IN CHEMISTRY
(2022)
Review
Cell Biology
Amrita Basu, Neil G. Patel, Elijah D. Nicholson, Ryan J. Weiss
Summary: Glycosaminoglycans (GAGs) are long polysaccharides found on the cell surface and extracellular matrix of animal cells, and play important roles in cellular processes and diseases. GAGs are complex molecules with extensive structural and functional heterogeneity, and their biosynthesis is a non-template driven process involving a group of enzymes. Due to their key roles in cell homeostasis and disease, targeting the assembly and function of GAGs is of great interest as a therapeutic approach.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Anil K. Gorle, Thomas Haselhorst, Samantha J. Katner, Arun Everest-Dass, James D. Hampton, Erica J. Peterson, Jennifer E. Koblinski, Eriko Katsuta, Kazuaki Takabe, Mark von Itzstein, Susan J. Berners-Price, Nicholas P. Farrell
Summary: The 1:1 adduct of the pentasaccharide Fondaparinux and the substitution-inert polynuclear platinum complex TriplatinNC was found to modulate the geometry around glycosidic linkages, potentially inhibiting heparan sulfate cleavage in breast cancer cells and metastasis in an animal model. This study provides insights into a novel approach for designing platinum drugs with intrinsic anti-metastatic potential.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Medicinal
Anna Egorova, Elke Bogner, Elena Novoselova, Kimberley M. Zorn, Sean Ekins, Vadim Makarov
Summary: Viruses as obligate intracellular parasites have evolved to enter host cells by first coming into contact through an initial adhesion, with some using heparan sulfate proteoglycans for this purpose. Inhibition of this early infection event by synthetic molecules has always been a target for medicinal chemists. Compounds based on the dispirotripiperazine scaffold have shown promise in preventing virus entry and replication.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Sam Spijkers-Shaw, Katrin Campbell, Nicholas J. Shields, John H. Miller, Phillip M. Rendle, Wanting Jiao, Sarah L. Young, Olga Zubkova
Summary: The synthesis and testing of a novel library of single entity trimer glycolipid mimetics that effectively inhibit HPSE at low nanomolar concentrations are reported. Preclinical tests showed that these mimetics can effectively inhibit tumor growth at low concentrations.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Samuel G. Holmes, Umesh R. Desai
Summary: Although molecular docking remains challenging for glycosaminoglycans (GAGs) due to their flexibility and anionic character, using a semi-rigid docking protocol can better reproduce the native topology of heparin/heparan sulfate (Hp/HS). Rigid and semi-rigid protocols are more accurate in predicting longer chain poses, while the semi-rigid approach is better for 2-4-mer poses. The new semi-rigid protocol, combined with a new computational parameter, shows promising potential for high-throughput screening of GAG sequences and identifying drug targets and drug-like Hp/HS sequences.
Article
Cell Biology
Yulu Cherry Liu, Bradley M. Wierbowski, Adrian Salic
Summary: Glypicans are important in multiple cell signaling pathways, but their relationship between structure and function is not yet clear. The study found that glypican 3 plays a regulatory role in Hedgehog signaling, and the purified ectodomain of glypican 3 can rescue signaling. The modified stalk with heparan sulfate is necessary and sufficient for this activity.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Maria Ennemoser, Alexandra Pum, Andreas Kungl
Summary: This review investigates the connection between modifications of GAG sulfation patterns and a wide range of pathological conditions, mainly focusing on a range of chronic diseases of the central nervous system (CNS) as well as the respiratory tract.
CARBOHYDRATE RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Rio S. Boothello, Nehru Viji Sankaranarayanan, Jyothi C. Sistla, Balaji Nagarajan, Chetna Sharon, John E. Chittum, Rabiya Y. Niyaz, Swarnali Roy, Aditi Nandi, Connor P. O'Hara, Rahaman Navaz Gangji, Daniel K. Afosah, Ravikumar Ongolu, Bhaumik B. Patel, Umesh R. Desai
Summary: This study reveals the inhibitory effect of shorter soluble heparan sulfate sequences on IGF-1R, contrary to the traditional relationship. Smaller oligosaccharides competitively bind in a unique pocket in the IGF-1R structure, inhibiting its activation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Biochemistry & Molecular Biology
Harkanwalpreet Sodhi, Alyssa Panitch
Summary: Glycosaminoglycans play a crucial role in tissue engineering by driving stem cell fate and promoting cell proliferation, and recent studies have explored their use in tissue constructs. The research trends in this area are evaluated, providing insights into future directions.
Article
Chemistry, Multidisciplinary
Joseph Wakpal, Vishaka Pathiranage, Alice R. Walker, Hien M. Nguyen
Summary: This article describes a method for synthesizing a library of HS mimetics from natural aminoglycosides, reducing the number of steps compared to traditional methods. Computational modeling was used to identify a new class of trisaccharide compounds derived from tobramycin that mimic natural HS and have a strong binding to heparanase but a low affinity for off-target platelet factor-4 protein.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Analytical
Zhangjie Wang, Katelyn Arnold, Vijay M. Dhurandahare, Yongmei Xu, Vijayakanth Pagadala, Erick Labra, Walter Jeske, Jawed Fareed, Marla Gearing, Jian Liu
Summary: This study describes a LC-MS/MS-based method to analyze the structural motifs of 3-O-sulfated heparan sulfate (HS). The method was used to determine the levels of 3-O-sulfated HS in pharmaceutical heparin and human brain. The study found that a specific 3-O-sulfated structural motif, tetra-1, was elevated in the brain HS from Alzheimer's disease patients.
ANALYTICAL CHEMISTRY
(2022)
Correction
Chemistry, Analytical
Zhangjie Wang, Katelyn Arnold, Vijay M. Dhurandhare, Yongmei Xu, Vijayakanth Pagadala, Erick Labra, Walter Jeske, Jawed Fareed, Marla Gearing, Jian Liu
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kunli Liu, Xuefei Huang
Summary: Hyaluronan nanoparticles (HA-NPs) have gained increasing interest for targeted imaging and therapy. By utilizing the interaction between HA and CD44, as well as the enhanced permeability and retention (EPR) effect, selective accumulation of HA-NPs at disease sites can be achieved. This review focuses on the synthesis strategies of HA-NPs and their applications in therapy and biomedical imaging.
CARBOHYDRATE RESEARCH
(2022)
Review
Cell Biology
Jian Liu, Lars C. Pedersen
Summary: This article summarizes the recent progress in substrate specificity studies of different 3-O-sulfotransferase isoforms and introduces a newly developed method for analyzing the level of 3-O-sulfated heparan sulfate using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Kedar N. Baryal, Sherif Ramadan, Guowei Su, Changxin Huo, Yuetao Zhao, Jian Liu, Linda C. Hsieh-Wilson, Xuefei Huang
Summary: A divergent approach was used to synthesize a library of HS tetrasaccharides that covered all possible sulfation structures. This library helped identify the structural requirements for HS sequences to bind to fibroblast growth factor-2 and showed weak affinity for platelet factor-4. This could lead to the development of new HS-based therapeutics without the adverse effect of heparin-induced thrombocytopenia.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemical Research Methods
Aniwat Juhong, Bo Li, Cheng-You Yao, Chia-Wei Yang, Dalen W. Agnew, Yu Leo Lei, Xuefei Huang, Wibool Piyawattanametha, Zhen Qiu
Summary: Traditionally, high-performance microscopes are required for high-resolution imaging, but the resulting images are typically large and not easily managed or stored. This study demonstrates custom convolution neural networks (CNNs) for super-resolution image enhancement and characterization of breast cancer histopathological images. The results show improved image quality and segmentation compared to other methods.
BIOMEDICAL OPTICS EXPRESS
(2023)
Article
Chemistry, Multidisciplinary
Mengxia Sun, Chi Zhang, Dexin Sui, Canchai Yang, Dohun Pyeon, Xuefei Huang, Jian Hu
Summary: Phosphatidylinositol phosphate kinases (PIPKs) are enzymes that produce lipid signaling molecules and have become attractive drug targets for various diseases. Researchers have designed and synthesized D-galactosyl lysophospholipids, which can selectively target phosphatidylinositol 4-phosphate 5-kinase. This study also discovered a human PIKfyve inhibitor that enhances the inhibition of Apilimod, an ATP-competitive PIKfyve inhibitor, in clinical trials for SARS-CoV-2 infection and amyotrophic lateral sclerosis. These findings demonstrate the potential of D-galactose-based phosphoinositide mimetics as artificial substrates and inhibitors of PIPKs.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Yanan Gao, Wei Wang, Yunru Yang, Qingyu Zhao, Chendong Yang, Xiaoying Jia, Yang Liu, Minmin Zhou, Weihong Zeng, Xuefei Huang, Sandra Chiu, Tengchuan Jin, Xuanjun Wu
Summary: Researchers have developed functionalized nanoparticles as a universal vaccine design platform for major diseases such as cancer and COVID-19. The nanoparticles induce potent immune responses and provide effective protection against tumors and the SARS-CoV-2 virus.
Article
Chemistry, Multidisciplinary
Lei Wang, Alexander W. Sorum, Bo-Shun Huang, Mallory K. Kern, Guowei Su, Nitin Pawar, Xuefei Huang, Jian Liu, Nicola L. B. Pohl, Linda C. Hsieh-Wilson
Summary: Glycosaminoglycans (GAGs) are complex carbohydrates in biology, and their biological roles and structure-function relationships are not well understood. Synthesizing large collections of structurally diverse GAG oligosaccharides would provide valuable insights and advancements in glycoscience. A new platform for synthesizing heparan sulfate (HS) oligosaccharide libraries displaying comprehensive sulfation patterns was developed, enabling the generation of a complete library of diverse HS oligosaccharides. These structures offer a unique perspective on the sulfation code of GAGs and identify sequences for modulating the activities of important growth factors and chemokines.
Article
Multidisciplinary Sciences
Huiqian Huang, Amelie M. Joffrin, Yuan Zhao, Gregory M. Miller, Grace C. Zhang, Yuki Oka, Linda C. Hsieh-Wilson
Summary: This study demonstrates that 4-O-sulfated chondroitin sulfate polysaccharides play a critical role in the regulation of perineuronal nets (PNNs) and synapse development in the mouse hippocampus, impacting anxiety and cognitive functions such as social memory. Alterations in CS 4-O-sulfation lead to imbalanced synaptic ratios, elevated anxiety levels, and social memory dysfunction. Modulating CS 4-O-sulfation levels reversibly affects PNN densities and the balance of excitatory and inhibitory synapses. Targeting CS 4-O-sulfation may offer therapeutic potential for addressing neuropsychiatric and neurodegenerative diseases associated with social cognitive dysfunction.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Engineering, Electrical & Electronic
Aniwat Juhong, Bo Li, Cheng-You Yao, Chia-Wei Yang, Kunli Liu, Dalen W. Agnew, Yu Leo Lei, Gary D. Luker, Harvey Bumpers, Xuefei Huang, Wibool Piyawattanametha, Zhen Qiu
Summary: Near-infrared (NIR) fluorescence imaging is proven to be useful in medical applications, especially image-guided surgery. We introduce a low-cost and portable NIR fluorescence imaging system that utilizes Nyxel(R) technology to improve quantum efficiency in the NIR range. By conjugating ICG with nanoworm particles (NWs-ICG), our system shows impressive applications in ex vivo tissues and in vivo image-guided surgery for breast tumors.
IEEE PHOTONICS TECHNOLOGY LETTERS
(2023)
Article
Biochemical Research Methods
Aniwat Juhong, Bo Li, Yifan Liu, Cheng-You Yao, Chia-Wei Yang, Dalen W. Agnew, Yu Leo Lei, Gary D. Luker, Harvey Bumpers, Xuefei Huang, Wibool Piyawattanametha, Zhen Qiu
Summary: Multispectral optoacoustic tomography (MSOT) is a useful technique for detailed analysis of biological samples, but it's time-consuming. This study proposes a deep learning model based on hybrid recurrent and convolutional neural networks to generate sequential cross-sectional images for MSOT. By using a larger step size for input images, the proposed model can generate additional high-resolution images, reducing acquisition time by approximately 71%.
JOURNAL OF BIOPHOTONICS
(2023)
Article
Materials Science, Biomaterials
Huiling Dong, Xuefei Huang, Xuanjun Wu
Summary: 9-SH-Sia is coupled to CPT to form a novel CPT prodrug (CPT-ss-Sia) that self-assembles into nanostructures in an aqueous solution. CPT-ss-Sia exhibits enhanced water solubility, GSH-triggered CPT release, and increased E-lactone ring stability, with comparable cancer cell-killing ability to CPT. Intravenous administration of CPT-ss-Sia inhibits tumor growth and reduces lesions without adverse effects on body weight in mice. This is the first report of the 9-SH-Sia conjugate-based prodrug, with broad clinical application prospects.
BIOMATERIALS SCIENCE
(2023)
Article
Chemistry, Organic
Sherif Ramadan, Guowei Su, Kedar Baryal, Linda C. Hsieh-Wilson, Jian Liu, Xuefei Huang
Summary: This study reports an automated machine-aided solid-phase strategy for the assembly of HS disaccharides, which significantly improves the synthesis efficiency. A diverse HS disaccharide library with different sulfation patterns was successfully prepared using this method.
ORGANIC CHEMISTRY FRONTIERS
(2022)
