Article
Biochemistry & Molecular Biology
Bichen Zhang, Kalina Lapenta, Qi Wang, Jin Hyun Nam, Dongjun Chung, Marie E. Robert, Michael H. Nathanson, Xiaoyong Yang
Summary: The study revealed that in the process of liver fibrosis caused by liver cell damage, OGT-deficient hepatocytes secrete TFF2, which activates HSCs and promotes fibrogenesis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Xing-Yong Liang, Jing Yang, Zhong-Hao Qiu, Lei Wang, Todd L. Lowary, Hua-Jun Shawn Fan
Summary: This study developed a method for preparing 2-deoxy-2-azido-alpha-D-galactopyranosidic bonds using donor 5, which exhibited good to excellent alpha-selectivity attributed to specific protecting groups. The presence of TBDPS on 3-O and benzylidenyl on 4,6-di-O enhanced the activity of the thioglycoside and improved stereoselectivity, as demonstrated through the synthesis of a alpha-galactosamine-containing pentasaccharide 26.
CARBOHYDRATE RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Yuan Chen, Noah R. Sundah, Nicholas R. Y. Ho, Auginia Natalia, Yu Liu, Qing Hao Miow, Yu Wang, Darius L. L. Beh, Ka Lip Chew, Douglas Chan, Paul A. Tambyah, Catherine W. M. Ong, Huilin Shao
Summary: This technology utilizes molecular nanotechnology to directly and programmably detect SARS-CoV-2 RNA targets in native patient specimens, achieving direct and sensitive RNA detection, fast response time, and robust programmability.
Article
Chemistry, Multidisciplinary
Fares Saidi, Oscar Javier Gamboa Marin, Jose Ignacio Veytia-Bucheli, Evgeny Vinogradov, Gokulakrishnan Ravicoularamin, Nicolas Y. Jolivet, Ahmad A. Kezzo, Eric Ramirez Esquivel, Adyasha Panda, Gaurav Sharma, Stephane P. Vincent, Charles Gauthier, Salim T. Islam
Summary: The combination of metabolic labeling and dick chemistry allows selective imaging of the surfaces of bacteria. In this study, researchers explored the feasibility of labeling the lipopolysaccharide (LPS) of Myxococcus xanthus using azido analogues of 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo). The results show that different azido analogues have varying effects on the growth and motility of the bacteria, providing important insights into the fundamental principles of outer membrane dynamics in live bacterial cells.
Article
Chemistry, Organic
Suvendu Halder, Rupa Bai Addanki, Bikash K. Sarmah, Pavan K. Kancharla
Summary: 2-Deoxy glycosyl ortho-[1-(p-MeOPhenyl)Vinyl]Benzoates (PMPVB) are stable and reactive glycosyl donors, which can be used for the synthesis of 2-deoxy alpha-glycosides with high stereocontrol under Bronsted acid conditions. The high stereoselectivities observed were discussed in relation to the relative free energy differences between the reactive intermediates.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
A. I. Tokatly, D. Z. Vinnitsky, A. A. Kamneva, D. V. Yashunsky, Y. E. Tsvetkov, N. E. Nifantiev
Summary: Glycosylation reactions using phenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-1-seleno-alpha-D-glucopyranoside and phenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-1-seleno-alpha-D-mannopyranoside with primary and secondary alcohols showed high yields and good alpha-stereoselectivity. The glycosylation with the glucopyranoside produced 2-azido-2-deoxyglucosides, while glycosylation with the mannopyranoside exclusively gave alpha-linked 2-azido-2-deoxymannosides.
RUSSIAN CHEMICAL BULLETIN
(2023)
Article
Biotechnology & Applied Microbiology
Shubham Parashar, Charu Chauhan, Abhiraj Rajasekharan, Jyoti Rautela, Tanya Jain, Kaisar Raza
Summary: In this study, two methods for fabricating Ac(4)2AzGlc-loaded PLGA nanoparticles were investigated, and a novel method for collecting the synthesized nanoparticles was proposed. The results showed that the nanoparticles were spherical in shape with uniform size and acceptable polydispersity indices. Preliminary experiments demonstrated efficient engineering of the nanoparticles in cells and animals, but further investigations are needed for confirmation.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kyriakos N. Papanicolaou, Jessica Jung, Deepthi Ashok, Wenxi Zhang, Amir Modaressanavi, Eddie Avila, D. Brian Foster, Natasha E. Zachara, Brian O'Rourke
Summary: O-GlcNAcylation plays a crucial role in regulating the activity of Erk1/2 and p38 MAPKs, thus affecting the signaling pathways involved in hypertrophic growth responses in cardiomyocytes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Colin D. Douglas, Lia Grandinetti, Nicole M. Easton, Oliver P. Kuehm, Joshua A. Hayden, Meghan C. Hamilton, Martin St Maurice, Stephen L. Bearne
Summary: 2-FPBA is shown to be a potent reversible, slow-onset inhibitor of mandelate racemase (MR), forming a benzoxaborole through intramolecular cyclization due to the N-zeta-B dative bond formation between Lys 166 and 2-FPBA. The structure of the resulting product when using o-carbonyl arylboronic acid reagents to modify proteins depends on the protein architecture at the site of modification.
Article
Biochemical Research Methods
Fei-fan He, Yi-yao Xin, Yuan-xin Ma, Shun Yang, Hui Fei
Summary: The research on the DERA enzyme in psychrophilic bacteria has shown that mutants like G189R and V66K exhibit higher catalytic activity towards specific substrates, providing an effective strategy for enhancing DERA activity. These mutants also show increased activity in condensation reactions without significant decline in aldehyde tolerance compared to the wild type.
PROTEIN EXPRESSION AND PURIFICATION
(2021)
Article
Biochemistry & Molecular Biology
Samy Cecioni, Roger A. Ashmus, Pierre-Andre Gilormini, Sha Zhu, Xi Chen, Xiaoyang Shan, Christina Gros, Matthew C. Deen, Yang Wang, Robert Britton, David J. Vocadlo
Summary: Understanding the function and regulation of enzymes within cells requires quality tools to report their activities. This article introduces a strategy for quantitatively monitoring enzyme activities within live cells and describes the design and synthesis of fluorescence-quenched substrates for sensitive quantitation. The substrates can be used to measure the engagement of target enzymes by inhibitors and the efficiency of pharmacological chaperones, highlighting the importance of quantifying activity within cells.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Matthew G. Alteen, Hayden Peacock, Richard W. Meek, Jil A. Busmann, Sha Zhu, Gideon J. Davies, Hiroaki Suga, David J. Vocadlo
Summary: This study applied an mRNA display technology with genetic code reprogramming to identify macrocyclic peptides that can inhibit O-GlcNAc transferase (OGT) activity. These macrocycles bind to the tetratricopeptide repeats of OGT and inhibit its activity through an allosteric mechanism. The high potency and novel mechanism of action of these OGT ligands may contribute to further understanding the specificity and regulation of OGT.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Gareth G. G. Doherty, Geraldine Jia Ming Ler, Norbert Wimmer, Paul V. V. Bernhardt, Roger A. A. Ashmus, David J. J. Vocadlo, Zachary Armstrong, Gideon J. J. Davies, Marco Maccarana, Jin-ping Li, Yasmin Kayal, Vito Ferro
Summary: The synthesis of Azasugar analogues of l-IdoA and d-GlcA, along with their enantiomers, as potential pharmacological chaperones for MPS I was conducted. X-ray crystallographic analysis confirmed the structures of these compounds. Although inactive against IDUA, compound 8 with l-IdoA configuration moderately inhibited beta-GLU. Compound 9 with d-GlcA configuration was a potent inhibitor of beta-GLU and a moderate inhibitor of heparanase. Co-crystallization of 9 with heparanase revealed close interactions between the endocyclic nitrogen of 9 and both the catalytic acid and catalytic nucleophile.
Article
Chemistry, Multidisciplinary
Roger A. Ashmus, Yang Wang, Manuel Gonzalez-Cuesta, Dustin T. King, Ben Tiet, Xi Chen, Yanping Zhu, Bryce Kirk, Jose M. Garcia Fernandez, Carmen Ortiz Mellet, Robert Britton, David J. Vocadlo
Summary: Glycoside hydrolases (GHs) are enzymes that play a role in various diseases. Researchers are searching for selective GH inhibitors to understand their functions and explore their therapeutic potential. In this study, a concise synthesis of iminosugar inhibitors of α-N-acetyl-galactosaminidase (α-NAGAL) was described. The newly synthesized inhibitor DGJNGuan exhibited potent and selective inhibition of α-NAGAL both in vitro and within cells, making it a useful tool compound for studying the physiological roles of α-NAGAL.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Wai Hang Cheng, Honor Cheung, Amy Kang, Jianjia Fan, Jennifer Cooper, Mehwish Anwer, Carlos Barron, Anna Wilkinson, Grace Hu, Jefferey Yue, Peter A. Cripton, David J. Vocadlo, Cheryl L. Wellington
Summary: This study investigated the effects of single high-energy traumatic brain injury (TBI) on tauopathy in a mouse model. The findings showed that TBI induced chronic white matter injury and altered GSK-3 fi activity, but did not cause significant changes in post-injury tauopathy in the brain tissue of rTg4510 mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Dentistry, Oral Surgery & Medicine
T. M. Taira, E. S. Ramos-Junior, P. H. Melo, C. C. Costa-Silva, M. G. Alteen, D. J. Vocadlo, W. B. Dias, F. Q. Cunha, J. C. Alves-Filho, K. Soe, S. Y. Fukada
Summary: Osteoclasts are important in bone mass regulation and have high metabolic activity. The study shows that metabolic reprogramming towards the hexosamine biosynthetic pathway (HBP) is necessary for osteoclast differentiation and determining bone resorption modes. In addition, O-GlcNAcylation facilitates aggressive trench resorption in human cells.
JOURNAL OF DENTAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Alexandra Gehrlein, Vinod Udayar, Nadia Anastasi, Martino L. L. Morella, Iris Ruf, Doris Brugger, Sophia von der Mark, Ralf Thoma, Arne Rufer, Dominik Heer, Nina Pfahler, Anton Jochner, Jens Niewoehner, Luise Wolf, Matthias Fueth, Martin Ebeling, Roberto Villasenor, Yanping Zhu, Matthew C. C. Deen, Xiaoyang Shan, Zahra Ehsaei, Verdon Taylor, Ellen Sidransky, David J. J. Vocadlo, Per-Ola Freskgard, Ravi Jagasia
Summary: The authors demonstrate that the transferrin receptor pathway can be therapeutically exploited to target lysosomal GCase deficiency, by using a fusion protein comprising GCase and a transferrin receptor antibody fragment. This has potential implications in treating GBA1-associated lysosomal dysfunction and may open a promising treatment paradigm for lysosomal storage diseases.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Edwin E. E. Escobar, Erin H. H. Seeley, Jesus E. Serrano-Negron, David J. J. Vocadlo, Jennifer S. S. Brodbelt
Summary: Post-translational O-glycosylation of proteins with N-acetylglucosamine is a cellular regulator linked to cancer. Mass spectrometry imaging is used to visualize the location of this sugar in primary tumor sections. O-GlcNAc hydrolase is employed for on-tissue hydrolysis of this sugar, providing additional evidence implicating it in tumor growth.
Article
Biochemistry & Molecular Biology
Sandeep Bhosale, Matthew C. Deen, Cameron Proceviat, Andrew Hettle, Dana K. Winter, Jacob Brockerman, Marina Levene, Andrew J. Bennet, Claude Spino, Alisdair B. Boraston, David J. Vocadlo
Summary: Trimming of host glycans is a common mechanism used by both commensal and pathogenic microflora for colonization. Streptococcus pneumoniae, an opportunistic Gram-positive bacterium, employs glycan processing enzymes and the exo-mannosidase SpGH92 as a virulence factor. The synthesis of a fluorogenic disaccharide substrate and the identification of a potential inhibitor for SpGH92 are reported.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Cecile Bousch, Brandon Vreulz, Kartikey Kansal, Ali El-Husseini, Samy Cecioni
Summary: Glycan recognition by glycan-binding proteins is crucial in biology, and photoaffinity labeling is an important method for capturing non-covalent interactions. This study presents a novel fluorinated azido-coumarin scaffold that enables fast and mild photolabeling, leaving a fluorescent tag on the crosslinked species. By coupling this scaffold to an alpha-fucoside, the researchers demonstrate fluorogenic photolabeling of glycan-protein interactions with varied affinities. This strategy and these fluoro-crosslinkers have the potential to be widely used for traceable capture of non-covalent binding events.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Sha Zhu, Matthew C. Deen, Yanping Zhu, Pierre-Andre Gilormini, Xi Chen, Oliver B. Davis, Marcus Y. Chin, Anastasia G. Henry, David J. Vocadlo
Summary: Fluorogenic substrates are useful for studying enzymatic processes within live cells, but they are incompatible with cellular fixation. However, a new substrate called LysoFix-GBA has been developed, which allows the chemical fixation of the substrate and enables quantification of glucocerebrosidase (GCase) activity in both live and fixed cells. This tool can be used to study the role of GCase activity in Parkinson's Disease and can serve as a foundation for creating fixable substrates for other lysosomal enzymes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Martin Calvelo, Alexandra Males, Matthew G. Alteen, Lianne I. Willems, David J. Vocadlo, Gideon J. Davies, Carme Rovira
Summary: This study reports the crystal structure of human O-linked beta-N-acetylglucosaminidase (hOGA) and elucidates its catalytic mechanism using QM/MM metadynamics. The enzyme can bind the substrate in either a chair- or a boat-like conformation, but only the latter is catalytically competent. These findings will aid in the development of more effective inhibitors for diseases associated with impaired O-GlcNAcylation.
Review
Biochemistry & Molecular Biology
Matthew C. Deen, Pierre-Andre Gilormini, David J. Vocadlo
Summary: Enzymes within cells are regulated by various factors, and monitoring enzyme activities in tissues is crucial in cell biology and disease etiology. The use of synthetic substrates and imaging modalities has great potential in detecting and quantifying enzyme activities. This article describes the latest developments in creating substrates for imaging glycoside hydrolase activities in mammalian systems, highlighting the limitations and challenges in the field, as well as prospects for overcoming them.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Sha Zhu, Matthew C. Deen, Yanping Zhu, Pierre-Andre Gilormini, Xi Chen, Oliver B. Davis, Marcus Y. Chin, Anastasia G. Henry, David J. Vocadlo
Summary: This study reports a simple method to chemically fix the LysoFix-GBA substrate, allowing quantification of GCase activity in live and fixed cells. It also enables co-localization studies and provides a tool for studying the role of GCase in Parkinson's Disease.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
