Article
Biochemistry & Molecular Biology
Helena Crijns, Lowie Adyns, Eva Ganseman, Seppe Cambier, Eline Vandekerckhove, Noemie Poertner, Lotte Vanbrabant, Sofie Struyf, Tanja Gerlza, Andreas Kungl, Paul Proost
Summary: This study investigated the interactions between glycosaminoglycans (GAGs) and proteins, as well as the structural requirements for binding. Through peptide design and experiments, it was found that the affinity and specificity of peptides for GAGs can be tuned by adapting their amino acid sequence and the number of GAG-binding motifs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Catarina Marques, Celso A. Reis, Romain R. Vives, Ana Magalhaes
Summary: Heparan Sulfate Proteoglycans (HSPGs) play important roles in orchestrating cellular events in physiology and pathology by modulating cell signaling networks and cell interactions. The structural features of HS chains are crucial for the functions of HSPGs, influencing protein interactions and signaling. The tightly controlled biosynthetic pathway of HS leads to structural diversity, which is differently regulated in various tissues, developmental stages, and pathologies such as cancer.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
John R. Couchman
Summary: Cell surface proteoglycans, such as syndecans, play crucial roles in regulating cell behavior, including interactions with extracellular matrix components and mediating proliferation, adhesion, and migration. In tumors, changes in the levels and distribution of syndecan-1 can have implications for prognosis, with loss of membrane staining and abnormal cytoplasmic or nuclear staining often indicating poor outcomes. Targeting syndecan-1 with antibody-toxin conjugates may hold promise for clinical applications in both myeloma and some carcinomas.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ayumu Mubuchi, Shoo Katsumoto, Makoto Tsuboi, Hideaki Ishikawa, Yoshihiro Nomura, Kyohei Higashi, Shinji Miyata
Summary: Chondroitin sulfate and heparan sulfate are sulfated glycosaminoglycan chains with different levels of sulfation and disaccharide compositions. The sulfated glycosaminoglycans from Perna canaliculus show potential as biomaterials for studying the structure-function relationships.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Dmitry K. Sokolov, Oleg B. Shevelev, Anna S. Khotskina, Alexandra Y. Tsidulko, Anastasia V. Strokotova, Galina M. Kazanskaya, Alexander M. Volkov, Evgenii E. Kliver, Svetlana V. Aidagulova, Evgenii L. Zavjalov, Elvira V. Grigorieva
Summary: Glioblastoma (GB) is an aggressive cancer with a high chance of recurrence, and the effects of chemotherapy drugs on heparan sulfate (HS) in brain tissue are still unknown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Microbiology
Carla Martin, Helena Ordiales, Francisco Vazquez, Marta Pevida, David Rodriguez, Jesus Merayo, Fernando Vazquez, Beatriz Garcia, Luis M. Quiros
Summary: This study found that cell surface glycosaminoglycans (GAGs) are involved in the adhesion of acne-related bacteria to skin cells, with different bacteria affecting different cell types. Bacterial adherence also led to changes in gene expression in skin cells, affecting the structure of GAG chains.
Review
Polymer Science
Qingchi Wang, Lianli Chi
Summary: This review investigates the structural alterations and roles of GAGs/PGs in various diseases, and discusses their potential in disease diagnosis, monitoring, prognosis, and drug development.
Article
Biochemical Research Methods
Gabor Toth, Domonkos Pal, Simon Sugar, Ilona Kovalszky, Katalin Dezso, Gitta Schlosser, Laszlo Drahos, Lilla Turiak
Summary: This study investigated the content and sulfation pattern of chondroitin sulfate (CS) and heparan sulfate (HS) in human hepatocellular carcinoma and cirrhotic liver tissues, considering the etiology of the diseases. Major differences were observed in the total abundance and sulfation pattern of CS and HS chains, providing important insights into the molecular mechanisms of chronic liver diseases.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sarah Y. Ebstein, Ashique Rafique, Yi Zhou, Amanda Krasco, Welby Montalvo-Ortiz, Lola Yu, Luisaidy Custodio, Rene C. Adam, Nicolin Bloch, Ken Lee, Funmilola Adewale, Dominic Vergata, Antonio Luz, Sebastien Coquery, Benjamin Daniel, Erica Ullman, Matthew C. Franklin, Aynur Hermann, Tammy Huang, William Olson, Samuel Davis, Andrew J. Murphy, Matthew A. Sleeman, Joyce Wei, Dimitris Skokos
Summary: VSIG4 is a complement receptor expressed on tissue resident macrophages and is involved in immune function. This study identifies heparan sulfates as novel binding partners of VSIG4 and suggests a role for them in immune modulation. Heparan sulfates compete with known VSIG4 binding partners and may play a role in the complex regulation of VSIG4 in the immune system.
Article
Clinical Neurology
Natalia Perez-Lopez, Carla Martin, Beatriz Garcia, Maria Pilar Solis-Hernandez, David Rodriguez, Ignacio Alcalde, Jesus Merayo, Ivan Fernandez-Vega, Luis M. Quiros
Summary: The saccharide chains of heparan sulfate play a crucial role in the pathogenesis of Alzheimer's disease, with differential transcription of biosynthetic genes observed in different brain regions and stages of AD pathology. The study revealed more alterations in gene transcription in moderate AD patients compared to mild cases, with fewer changes in genes related to early stages of synthesis in severe patients and an overexpression of late-stage genes. These alterations correlated with progressive brain atrophy, particularly in the cerebellum, and were consistent with immunohistochemical detection of certain heparan sulfate epitopes.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Anastasia V. Strokotova, Elvira V. Grigorieva
Summary: Glucocorticoids are commonly used to treat various diseases but can cause side effects. Recent studies suggest that the toxic effects of glucocorticoids on key extracellular components in the brain may be an underlying mechanism for these side effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Brigida Bochicchio, Giselle C. Yeo, Pearl Lee, Deniz Emul, Antonietta Pepe, Antonio Laezza, Nicola Ciarfaglia, Daniela Quaglino, Anthony S. Weiss
Summary: This study identifies novel cell-adhesive sites in the tropoelastin N-terminal region between domains 12 and 16, which interact with alpha V and alpha 5 beta 1 integrin receptors to facilitate cell attachment and spreading. The findings suggest that domains 12-16 of tropoelastin direct initial cell attachment through cell-surface heparan sulfate glycosaminoglycans, followed by integrin-promoted attachment and spreading, advancing our understanding of elastin matrix biology.
Article
Biochemistry & Molecular Biology
Zhengliang L. Wu, James M. Ertelt
Summary: The study focused on assays for endoglycosidases and demonstrated the substrate specificities and activities of HYALs under different pH conditions. It was also found that the activities of HYALs must be strictly regulated by pH levels. The research suggests the potential of designing novel therapeutics by targeting these important enzymes.
Article
Virology
Ritesh Tandon, Joshua S. Sharp, Fuming Zhang, Vitor H. Pomin, Nicole M. Ashpole, Dipanwita Mitra, Weihua Jin, Hao Liu, Poonam Sharma, Robert J. Linhardt, Martin G. McCandless
Summary: SARS-CoV-2 virus relies on spike glycoprotein for cell entry, and several sulfated polysaccharides have shown potent neutralizing effects against the virus, demonstrating potential prophylactic and therapeutic applications.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Balaji Nagarajan, Nehru Viji Sankaranarayanan, Umesh R. Desai
Summary: GAGs exhibit a high level of conformational and configurational diversity, but it remains underexplored in terms of protein recognition and modulation. Only a few therapeutics have been designed or discovered so far. Recent studies on chondroitin sulfate (CS) have led to the investigation of the conformational dynamism of CS building blocks using molecular dynamics (MD). The results suggest that CS building blocks offer unique conformational dynamism that may provide unique electrostatic surfaces for protein recognition.
Article
Biochemistry & Molecular Biology
Balaji Nagarajan, Samuel G. Holmes, Nehru Viji Sankaranarayanan, Umesh R. Desai
Summary: This article discusses the use of molecular dynamics (MD) to understand the properties of glycosaminoglycans (GAGs) in free solution and their interaction with proteins. The results of MD studies suggest that the recognition of GAGs by proteins varies from highly selective to fully non-selective, with intermediate levels of selectivity and plasticity.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(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)
Article
Chemistry, Medicinal
Shravan Morla, Ongolu Ravikumar, Connor O'Hara, Rio Boothello, Alberto Vera, Elsamani I. Abdelfadiel, Rawan Fayyad, Daniel K. Afosah, Chetna Sharon, Leopoldo Fernandez, Syed Ammer Shah, Bhaumik B. Patel, Umesh R. Desai
Summary: Conjugating cholesterol to synthetic sulfated glycosaminoglycan (GAG) mimetics enables oral delivery and shows excellent anticancer potential both in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Yoan Monneau, Cyrielle Arrault, Coraline Duroux, Marie Martin, Fabien Chirot, Luke Mac Aleese, Marion Girod, Clothilde Comby-Zerbino, Agnes Hagege, Olivier Walker, Maggy Hologne
Summary: Silver has been used as an antimicrobial agent, but some Gram-negative bacteria have developed resistance, leading to deaths in burn units. The protein SilE plays a crucial role in bacterial silver resistance. Through various techniques, it has been found that SilE consists of four helical segments and has four strong silver binding sites. These findings enhance our understanding of the mechanism of SilE in the silver efflux pump complex and aid in the development of inhibitors to combat bacterial silver resistance.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Medicinal
Elsamani I. Abdelfadiel, Rama Gunta, Bharath Kumar Villuri, Daniel K. Afosah, Nehru Viji Sankaranarayanan, Umesh R. Desai
Summary: Natural glycosaminoglycans (GAGs) are a diverse group of natural products that have not been fully utilized. Research has only led to the development of one GAG-like synthetic drug, highlighting the difficulty in working with GAGs. This Perspective aims to transform the negative perception of GAGs by highlighting recent advances in GAG mimetics, specifically in the design of synthetic sulfated small molecules as allosteric modulators of coagulation factors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Nagendraprabhu W. Ponnuraj, Haji Akbar, Justine F. Arrington, Stephen Spatz, Balaji F. Nagarajan, Umesh Desai, Keith F. Jarosinski
Summary: The study reveals that the conserved Herpesviridae protein kinase (CHPK) is a crucial factor for Marek's disease herpesvirus (MDV) in chicken infection, and the removal of the US10 protein from MDV reduces its virulence. Understanding these viral proteins and their functions during infection is important for elucidating the infection mechanism and developing therapeutic strategies.
Article
Biochemistry & Molecular Biology
Daniel K. Afosah, Rawan M. Fayyad, Valerie R. Puliafico, Spencer Merrell, Eltice K. Langmia, Sophie R. Diagne, Rami A. Al-Horani, Umesh R. Desai
Summary: Researchers identified a synthetic molecule, octasulfated di-quercetin NSGM 25, which effectively inhibits CatG as well as other pro-inflammatory proteases. NSGM 25 demonstrated no bleeding risk and could potentially be used for a multi-pronged anti-inflammatory approach in treating various inflammatory disorders.
Article
Biochemistry & Molecular Biology
Nehru Viji Sankaranarayanan, Srinivas Sistla, Balaji Nagarajan, John E. Chittum, Joseph T. Y. Lau, Umesh R. Desai
Summary: Using our in-house combinatorial virtual library screening (CVLS) technology, we discovered that glycosaminoglycans (GAGs) may interact with sialyl transferases (STs) to varying degrees. Our detailed CVLS and molecular dynamics studies found that the common hexasaccharide sequence of heparan sulfate (HS) preferentially binds to ST6GAL1. This novel finding is important for understanding the physiological/pathological consequences of modulating sialylation of glycan substrates on cells.
Meeting Abstract
Oncology
Connor O'Hara, Shravan Morla, Ravikumar Ongolu, Nirmita Patel, Rio Boothello, Bhaumik Patel, Umesh Desai
Meeting Abstract
Biochemistry & Molecular Biology
Daniel K. Afosah, Valerie Puliafico, Spencer Merrell, Eltice Langmia, Rawan Fayyad, Rami A. Al-horani, Umesh R. Desai
Meeting Abstract
Biochemistry & Molecular Biology
Michael E. Rusiniak, Nehru Viji Sankaranarayanan, Srinivas Sistla, Amy Freeland, John E. Chittum, Ding Xu, Karin Hoffmeister, Umesh R. Desai, Joseph T. Y. Lau
Article
Biochemistry & Molecular Biology
Samuel G. Holmes, Balaji Nagarajan, Umesh R. Desai
Summary: This study discovered novel compact topologies of heparan sulfate (HS) that are influenced by the 3-O-sulfation of cis-idoA residues. The transition in HS topology is driven by rotations that reduce like-charge repulsion, release water molecules, and establish specific interactions. These findings reveal a dynamic sulfation code in natural HS that could be utilized for selective recognition of target proteins.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)