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
Oncology
Miriam Gross-Cohen, Sari Feld, Gil Arvatz, Neta Ilan, Israel Vlodavsky
Summary: Hpa2, a close homolog of heparanase, plays a role in a rare genetic disease called urofacial syndrome, indicating its importance in protein coding; despite lacking HS-degrading activity, it shows a high affinity to HS; experimental evidence shows that Hpa2 affects cell adhesion, migration, and colony morphology.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Casper de Boer, Zachary Armstrong, Vincent A. J. Lit, Uri Barash, Gijs Ruijgrok, Ilanit Boyango, Merle M. Weitzenberg, Sybrin P. Schroder, Alexi J. C. Sarris, Nico J. Meeuwenoord, Pedro Bule, Yasmine Kayal, Neta Ilan, Jeroen D. C. Codee, Israel Vlodavsky, Herman S. Overkleeft, Gideon J. Davies, Liang Wu
Summary: Research has shown that by developing effective HPSE inhibitors, extracellular HPSE activity can be reduced, thereby reducing the aggressiveness of cancer and potentially controlling pathological HPSE-driven malignancies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Hematology
Raghuram Koganti, Abdullah Memon, Deepak Shukla
Summary: Heparan sulfate is a glycosaminoglycan found in mammalian tissues that contributes to the structural integrity of the extracellular matrix and cell signaling, but is also exploited by viruses during infection. Loss or inhibition of heparan sulfate proteoglycans during infection can lead to significant decreases in viral entry and infectivity, affecting multiple viruses such as herpesviruses, HIV, dengue virus, HPV, and coronaviruses.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2021)
Article
Chemistry, Multidisciplinary
Mohit Chhabra, Gareth G. Doherty, Nicholas W. See, Neha S. Gandhi, Vito Ferro
Summary: Heparan sulfate is a complex polysaccharide widely expressed on cell surfaces and in the extracellular matrix, interacting with numerous proteins to mediate various biological and pathological processes. Developing synthetically tractable HS mimetics with fewer side effects has become an attractive approach for treating cancer and infectious diseases.
Article
Chemistry, Multidisciplinary
Mohit Chhabra, Jennifer C. Wilson, Liang Wu, Gideon J. Davies, Neha S. Gandhi, Vito Ferro
Summary: This study investigates the interaction between Pixatimod and heparanase using a combination of NMR experiments and molecular modeling. The results show that Pixatimod can bind to the active site of heparanase in different conformations, effectively blocking the binding of its natural substrate. This study provides insights for the design of next-generation heparanase inhibitors and substrates.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Medicine, General & Internal
Elisabeth Zechendorf, Katharina Schroeder, Lara Stiehler, Nadine Frank, Christian Beckers, Sandra Kraemer, Michael Dreher, Alexander Kersten, Christoph Thiemermann, Gernot Marx, Tim-Philipp Simon, Lukas Martin
Summary: Heparanase activity and heparan sulfate levels correlate with the severity and outcomes of COVID-19, and may be helpful in predicting clinical progression and outcomes in patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Neurosciences
Xiao Zhang, Paul O'Callaghan, Honglian Li, Yingxia Tan, Ganlin Zhang, Uri Barash, Xiaomin Wang, Lars Lannfelt, Israel Vlodavsky, Ulf Lindahl, Jin-Ping Li
Summary: Defective clearance of amyloid-beta in the brain, caused by elevated levels of heparanase, results in impaired perivascular drainage and accumulation of A beta, contributing to the pathogenesis of Alzheimer's disease. This study highlights the potential role of heparanase in altering the blood-brain barrier and promoting amyloid-beta accumulation in the brain.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Review
Virology
Pankaj Sharma, Divya Kapoor, Deepak Shukla
Summary: This article discusses the role of HPSE and SDC-1 as newly identified host factors that facilitate HSV-1 release during infection.
Article
Biochemistry & Molecular Biology
Carina Mucciolo Melo, Helena Bonciani Nader, Giselle Zenker Justo, Maria Aparecida Silva Pinhal
Summary: Heparanase is an enzyme in mammals that cleaves heparan sulfate/heparin chains from proteoglycans. Experiments showed that exogenous heparin can increase Heparanase expression through the Wnt/beta-catenin pathway.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Zuopeng Wu, Rebecca A. Sweet, Gerard F. Hoyne, Charmaine J. Simeonovic, Christopher R. Parish
Summary: It has been accepted for decades that T lymphocytes and metastasising tumour cells traverse basement membranes (BM) by deploying a battery of degradative enzymes, particularly proteases. However, recent studies suggest that there are other mechanisms that allow cell migration through basement membranes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Alyce J. Mayfosh, Tien K. Nguyen, Mark D. Hulett
Summary: The extracellular matrix plays crucial roles in maintaining tissue structure, immune defense, and acting as a reservoir for bioactive molecules, with heparan sulfate proteoglycans (HSPGs) and their component heparan sulfate being essential in these processes. Understanding the regulation of heparanase and its downstream targets is important for potential therapeutic strategies in inflammatory diseases, atherosclerosis, fibrosis, and cancer metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Tien K. Nguyen, Stephanie Paone, Enoch Chan, Ivan K. H. Poon, Amy A. Baxter, Shane R. Thomas, Mark D. Hulett
Summary: Cardiovascular disease is the leading cause of death and disability worldwide, and atherosclerosis plays a crucial role in its development. Heparanase, as the only mammalian enzyme known to cleave heparan sulfate, has been found to be involved in various physiological and pathological processes, including inflammation and plaque formation. This review focuses on the emerging role of heparanase in atherosclerosis and provides an up-to-date overview of its functions.
Article
Biochemistry & Molecular Biology
Jia Shi, Riku Kanoya, Yurina Tani, Sodai Ishikawa, Rino Maeda, Sana Suzuki, Fumiya Kawanami, Naoko Miyagawa, Katsuhiko Takahashi, Teruaki Oku, Ami Yamamoto, Kaori Fukuzawa, Motowo Nakajima, Tatsuro Irimura, Nobuaki Higashi
Summary: This study found that sulfated hyaluronan can inhibit the enzymatic and biological actions of heparanase, a key enzyme involved in cancer malignancy and inflammation. Sulfated hyaluronan effectively inhibits the degradation of heparan sulfate by human and mouse heparanase, and it can bind to heparanase molecules. In the presence of sulfated hyaluronan, the invasion of heparanase-positive cells and the release of CCL2 are significantly suppressed. The inhibitory effect is likely due to competitive binding between sulfated hyaluronan and heparanase molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Applied
Shoichi Onishi, Kento Shionoya, Kazuki Sato, Ayumu Mubuchi, Shiori Maruyama, Tadaaki Nakajima, Masahiro Komeno, Shinji Miyata, Kazumi Yoshizawa, Takeshi Wada, Robert J. Linhardt, Toshihiko Toida, Kyohei Higashi
Summary: The study investigates the glycosaminoglycans (GAGs) derived from marine organisms and finds that marine invertebrates, especially Bivalvia, are rich sources of highly sulfated or branched GAGs. A novel fucosylated heparan sulfate (Fuc-HS) is identified from the midgut gland of the Japanese scallop, Patinopecten yessoensis. Scallop HS exhibits resistance to GAG-degrading enzymes and shows anti-coagulant and neurite outgrowth-promoting activities. These findings suggest that the midgut gland of scallops is a valuable source of biologically active Fuc-HS.
CARBOHYDRATE POLYMERS
(2023)