Article
Chemistry, Medicinal
Jeong Hyeon Cha, Eunsu Kim, Hyeong Ji Lee, Young-Ho Lee, Jeonghyun Lee, Eunha Kim, Chan Hyuk Kim
Summary: Metabolic glycan labeling combined with CAR-T cell therapy can provide novel cancer immunotherapy for solid tumors that lack viable target antigens.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Weizhi Yu, Jeremy M. Baskin
Summary: In this review, recent advances in understanding the mechanisms of diazirine photocrosslinking are summarized, and an overview of the latest applications of photoaffinity labeling in revealing the interactions between diverse types of lipids and specific members of the proteome is provided.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kathia Antillon, Patrick A. Ross, Mark P. Farrell
Summary: The abundance of sialic add-containing glycans in the glycocalyx of malignant cells enables immune evasion. In this study, researchers found that incorporating a chimeric antigen receptor (CAR) ligand into malignant cell glycans increased the susceptibility of malignant cells to CAR-expressing natural killer (NK) cells, thereby enhancing the cytolytic activity against malignant cells.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Taresh P. Khobragade, Sharad Sarak, Amol D. Pagar, Hyunwoo Jeon, Pritam Giri, Hyungdon Yun
Summary: In this study, a multi-enzyme cascade was developed for synthesizing the sitagliptin intermediate, achieving high conversion rates using whole-cell systems and optimized reaction parameters. Through screening and controlling enzyme expression levels, 70% of the sitagliptin intermediate was successfully produced on a gram scale.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Jodie Scache, Vincent Rigolot, Cedric Lion, Marlene Mortuaire, Tony Lefebvre, Christophe Biot, Anne-Sophie Vercoutter-Edouart
Summary: Sialylation of cell surface glycans is important for cell-cell interaction and communication with the microenvironment. A method called metabolic oligosaccharide engineering (MOE) can be used to study sialylation by incorporating unnatural monosaccharides into sialylated glycoconjugates and detecting them with a bioorthogonal ligation of a molecular probe. Among the bioorthogonal reactions, copper-catalyzed azide-alkyne cycloaddition (CuAAC) is the only ligation that allows both reactive tags to be switched on the chemical reporter or on the probe, making it a flexible and adaptable reaction. This study compared the efficiency of different chemical reporters in labeling sialoglycoproteins in human colon cell lines and found that switching the bioorthogonal tags greatly impacted the metabolic incorporation of the analogs. ManNAz was found to be the most versatile reporter for studying sialylation in these cells.
SCIENTIFIC REPORTS
(2022)
Article
Agriculture, Multidisciplinary
Mingli Zhao, Yingying Zhu, Hao Wang, Jiameng Zhang, Wei Xu, Wanmeng Mu
Summary: N-acetylneuraminic acid (NeuAc) is a predominant sialic acid in human cells and human milk, and it has great potential in the pharmaceutical, cosmetic, and food industries. Microbial synthesis using metabolic engineering strategies is an important approach to produce NeuAc on a large scale.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
David E. Scheim, Paola Vottero, Alessandro D. Santin, Allen G. Hirsh
Summary: According to biochemical properties, sialylated glycan attachments between SARS-CoV-2 spike protein and host cells play a key role in the virus's pathology. The virus can attach to and damage red blood cells, platelets, and endothelial cells. Risk factors for severe COVID-19, such as age, diabetes, and obesity, are associated with increased RBC clumping. Furthermore, differences in glycan attachment release between common cold strains and deadly coronaviruses have been identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Darlin Lantigua, Xinchen Wu, Sanika Suvarnapathaki, Michelle A. Nguyen, Gulden Camci-Unal
Summary: This study investigated the osteoinductive capacity of GelMA hydrogels containing bone meal powder particles, showing promising potential for enhancing bone formation. The scaffold displayed enhanced mechanical performance and promoted the differentiation of pre-osteoblast cells in vitro, while also demonstrating promising biocompatibility and biodegradation properties in vivo. The physical and biological properties of this biomaterial can be tuned based on the concentration of bone meal powder in GelMA scaffolds, offering a new composite scaffold for bone tissue engineering.
BIOENGINEERING-BASEL
(2021)
Article
Cell Biology
Xu Wang, Mingyue Liu, Jifeng Zhang, Nicholas K. Brown, Peng Zhang, Yan Zhang, Heng Liu, Xuexiang Du, Wei Wu, Martin Devenport, Weng Tao, Yang Mao-Draayer, Guo-Yun Chen, Y. Eugene Chen, Pan Zheng, Yang Liu
Summary: The study found that the CD24-Siglec-E axis can suppress obesity-related metabolic dysfunction, it is an important immune checkpoint against metaflammation and metabolic disorder.
Review
Biotechnology & Applied Microbiology
Huan Liu, Yuhan Jin, Renwei Zhang, Yuchen Ning, Yue Yu, Peng Xu, Li Deng, Fang Wang
Summary: Organic acids are important consumable materials with wide applications, and their global market is projected to reach $36.86 billion by 2026. To address environmental concerns and meet sustainable development goals, genetically-modified microbes are used for large-scale fermentative production of organic acids, replacing the traditional chemical catalysis process. However, low productivity has hindered the industrial-scale application of bio-based organic acids.
BIOTECHNOLOGY ADVANCES
(2023)
Article
Biochemistry & Molecular Biology
Henry Madubuike, Natalie Ferry
Summary: The demand for high-performance biocatalysts has been driven by the need for cleaner alternatives to current chemical syntheses. However, biocatalysts often exhibit low performance in industrial conditions. In this study, an engineered acetyl xylan esterase (BaAXE) was modified to improve its performance in a hydrophilic organic solvent. Rational design approach was used to introduce charged residues in the solvent-affecting region of the enzyme, resulting in mutants with improved activity and stability. Computational analysis revealed the role of novel intermolecular interactions in enhancing the performance of the mutants. This work supports the importance of protein engineering in optimizing the characteristics of wild-type enzymes.
Article
Biochemistry & Molecular Biology
Jeremias E. G. A. Dold, Valentin Wittmann
Summary: Metabolic glycoengineering (MGE) is a method utilized to incorporate chemical reporter groups into cellular glycans, allowing for visualization and isolation of glycans and potentially targeting drugs to cancer cells. The study introduced a new labeling reaction using 1,2-diamino-4,5-methylenedioxybenzene for quantification of sialic acid derivates after MGE. It also explored the effects of various ManNAc derivatives on sialic acid production in different cell types.
Article
Chemistry, Multidisciplinary
Casia L. Wardzala, Amanda M. Wood, David M. Belnap, Jessica R. Kramer
Summary: Mucins play an important role in coronavirus transmission, and their molecular structure plays a complex and significant role in host defense.
ACS CENTRAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Jiayu Sun, Zhimin Huang, Yifei Du, Pinou Lv, Xinqi Fan, Peng Dai, Xing Chen
Summary: It was found that per-O-acetylated clickable unnatural sugars used in metabolic glycan labeling (MGL) for analyzing glycans were cytotoxic to cultured primary neurons. This cytotoxicity was due to the non-enzymatic S-glyco-modification reactions of the sugars with protein cysteines, resulting in modified proteins associated with biological functions related to microtubule cytoskeleton organization and neuron projection development. By using S-glyco-modification-free unnatural sugars, MGL without cytotoxicity was established in cultured primary neurons, allowing for visualization of cell-surface sialylated glycans and large-scale identification of sialylated N-linked glycoproteins and modification sites.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lu Wang, Yufang Zhang, Yijing Xia, Changzhen Xu, Kejing Meng, Jing Lian, Xinsong Zhang, Jie Xu, Chunfang Wang, Bin Zhao
Summary: An injectable photocrosslinked methacrylylated silk fibroin/hyaluronic acid composite hydrogel has been developed for pulp regeneration in dentistry, with good biocompatibility and mechanical properties. The results indicate that cells in low-concentration RSFMA composite gel exhibit better growth, proliferation, and osteogenic differentiation ability.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Editorial Material
Biochemistry & Molecular Biology
Janet E. McCombs, Jay K. Kolls
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Susan Matthew, Qi-Yin Chen, Ranjala Ratnayake, Charles S. Fermaintt, Daniel Lucena-Agell, Francesca Bonato, Andrea E. Prota, Seok Ting Lim, Xiaomeng Wang, J. Fernando Diaz, April L. Risinger, Valerie J. Paul, Maria Angela Oliva, Hendrik Luesch
Summary: Research has identified a novel microtubule-destabilizing cyclodepsipeptide, gatorbulin-1 (GB1), produced by a marine cyanobacterium, which binds to a seventh binding site at the tubulin intradimer interface. Through multidimensional characterization and validation, the unique chemical and mechanistic novelty of GB1 has been elucidated, paving the way for new antitumoral pharmacological approaches.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Immunology
Joseph P. Hoffmann, Jay K. Kolls, Janet E. McCombs
Summary: Lower respiratory infections are a major cause of morbidity and mortality worldwide, exacerbated by antimicrobial resistance. ILC3s, recently discovered tissue resident innate immune cells, play important roles in regulating mucosal immunity and tissue homeostasis, particularly in responding rapidly to infections at mucosal sites.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nichole J. Pedowitz, Emma G. Jackson, Justin M. Overhulse, Charles E. McKenna, Jennifer J. Kohler, Matthew R. Pratt
Summary: Metabolic chemical reports have revolutionized the study of glycosylation, but they can lead to nonspecific S-glycosylation when administered as per-O-acetylated sugars. By synthesizing and characterizing reporter molecules functionalized with hexanoic acid, the researchers were able to reduce background labeling and nonspecific chemical labeling in cell lysates, providing a template for designing more reliable reporter molecules in the future.
ACS CHEMICAL BIOLOGY
(2021)
Article
Cell Biology
Jennifer J. Kohler
Summary: The study revealed that the modification of O-GlcNAc enhances permeability of the nuclear pore complex, speeding up transport in both directions.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Charles S. Fermaintt, Leila Takahashi-Ruiz, Huiyun Liang, Susan L. Mooberry, April L. Risinger
Summary: Microtubule-targeting agents, such as the microtubule destabilizer eribulin, can activate innate immune signaling pathways independently of their antimitotic effects, by accumulating cytoplasmic mitochondrial DNA.
MOLECULAR PHARMACOLOGY
(2021)
Article
Immunology
Naoki Iwanaga, Kong Chen, Haoran Yang, Shiping Lu, Joseph P. Hoffmann, Alanna Wanek, Janet E. McCombs, Kejing Song, Javier Rangel-Moreno, Elizabeth B. Norton, Jay K. Kolls
Summary: A vaccine composed of OmpX from Klebsiella pneumoniae and LTA1 adjuvant administered intrapulmonary can induce T(H)1 and T(H)17 cells that share transcriptional features with cells elicited by heat-killed K. pneumoniae, showing promising results in promoting immunity to K. pneumoniae.
SCIENCE IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Emma G. Jackson, Giuliano Cutolo, Bo Yang, Nageswari Yarravarapu, Mary W. N. Burns, Ganka Bineva-Todd, Chloe Roustan, James B. Thoden, Halley M. Lin-Jones, Toin H. van Kuppevelt, Hazel M. Holden, Benjamin Schumann, Jennifer J. Kohler, Christina M. Woo, Matthew R. Pratt
Summary: Bio-orthogonal chemistries have revolutionized various fields, with metabolic chemical reporters (MCRs) playing a crucial role in incorporating bio-orthogonal functionalities into biomolecules. Research on selective MCRs provides insights into understanding intracellular glycosylation modifications.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Daniela J. Carroll, Mary W. N. Burns, Lynda Mottrarn, Daniel C. Propheterl, Andrew Boucher, Gabrielle M. Lessen, Ashwani Kumar, Stacy A. Malaker, Chao Xing, Lora Hooper, Ulf Yrlid, Jennifer J. Kohler
Summary: IL-22 signaling regulates fucosylation of glycoproteins in intestinal epithelial cells by regulating the expression of B3GNT7, which is involved in the synthesis of polyLacNAc chains. This study uncovers a novel role for B3GNT7 in intestinal fucosylation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Badrinath N. Kakde, Emanuela Capota, Jennifer J. Kohler, Uttam K. Tambar
Summary: We reported a robust and stereoselective synthesis of cell-permeable GIcNAc-1-phosphate esters based on commercially available bis(diisopropylamino)-chlorophosphine, applying this method to two diazirine-containing GlcNAc analogues and demonstrating successful cellular incorporation of these compounds to support photo-cross-linking applications.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemical Research Methods
Nageswari Yarravarapu, Rohit Sai Reddy Konada, Narek Darabedian, Nichole J. Pedowitz, Soumya N. Krishnamurthy, Matthew R. Pratt, Jennifer J. Kohler
Summary: Glycan binding is crucial in extracellular recognition events. This method utilizes exoenzymatic labeling to add a modified sialic acid to cell surface glycoconjugates, enabling UV-induced crosslinking of glycan-mediated binding interactions.
BIOCONJUGATE CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Mary W. N. Burns, Jennifer J. Kohler
Summary: Glycoconjugates are assembled by the coordinated actions of glycosyltransferases and glycosidases. Mutagenesis can be used to introduce unnatural sugar analogs for labeling and isolating substrates, and engineering enzymes can help determine the roles of specific glycosylation events. The engineering of glycosidases can also be used to target specific substrates, with applications in both basic science and translational research.
ISRAEL JOURNAL OF CHEMISTRY
(2023)
Letter
Biochemistry & Molecular Biology
Michael Boyce, Stacy A. Malaker, Nicholas M. Riley, Jennifer J. Kohler
Article
Biochemistry & Molecular Biology
Akshi Singla, Andrew Boucher, Kerri-Lee Wallom, Michael Lebens, Jennifer J. Kohler, Frances M. Platt, Ulf Yrlid
Summary: Prior research on cholera toxin (CT) binding and intoxication has relied on human colonic cancer derived epithelial cells. However, this study used human enteroids derived from jejunal biopsies to study CT binding and intoxication of human non-transformed small intestinal epithelial cells. The study found that inhibition of fucosylation or O-glycosylation sensitized enteroids to CT intoxication. Furthermore, simultaneous inhibition of fucosylation and O-glycosylation increased the availability of additional glycoconjugates, but counteracted the sensitization in CT intoxication caused by inhibiting O-glycosylation due to reduction in fucose. This suggests a dual role of fucose in influencing CT binding and intoxication. Additionally, the study revealed a role for human genetic variation in determining sensitivity to CT.
Article
Biochemistry & Molecular Biology
Han Wu, Asif Shajahan, Jeong-Yeh Yang, Emanuela Capota, Amberlyn M. Wands, Connie M. Arthur, Sean R. Stowell, Kelley W. Moremen, Parastoo Azadi, Jennifer J. Kohler
Summary: This study describes a metabolic method to introduce a photo-cross-linker onto GlcNAc residues of cell-surface N-linked glycoproteins, which can be used to discover and characterize binding interactions that depend on N-glycans.
CELL CHEMICAL BIOLOGY
(2022)
