Article
Chemistry, Multidisciplinary
Hendrik Hessefort, Angelina Gross, Simone Seeleithner, Markus Hessefort, Tanja Kirsch, Lukas Perkams, Klaus Ole Bundgaard, Karen Gottwald, David Rau, Christopher Guenther Franz Graf, Elisabeth Rozanski, Sascha Weidler, Carlo Unverzagt
Summary: The in-vivo activity of EPO is carbohydrate-dependent, with the number of sialic acid residues regulating its circulatory half-life. A chemoenzymatic approach was developed for obtaining glycoforms of EPO with and without sialic acids. Synthetic EPOs showed biological recognition by forming 1:1 complexes with recombinant EPO receptor.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Andreas Reif, Kevin Lam, Sascha Weidler, Marie Lott, Irene Boos, Juliane Lokau, Christian Bretscher, Manuel Moennich, Lukas Perkams, Marina Schmaelzlein, Christopher Graf, Jan-Patrick Fischer, Carolin Lechner, Kerstin Hallstein, Stefan Becker, Michael Weyand, Clemens Steegborn, Gerhard Schultheiss, Stefan Rose-John, Christoph Garbers, Carlo Unverzagt
Summary: A library of glycoforms of human interleukin 6 (IL-6) was generated using semisynthesis, and their in vivo plasma clearance rates in rats were evaluated. The results showed that IL-6 glycoforms with different structures exhibited varying clearance rates in the body, with 2,6-sialylated glycoforms of IL-6 being cleared faster in most cases.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Polymer Science
Marie Rosselin, Zoeisha S. Chinoy, Lourdes Monica Bravo-Anaya, Sebastien Lecommandoux, Elisabeth Garanger
Summary: The study showed that the presence of a linker at the anomeric position of galactose and the absence of positive charge on the polypeptide residue holding the sugar unit were critical for binding to RCA120 in the synthetic elastin-like glycopolypeptides library.
Article
Chemistry, Multidisciplinary
Farong Ye, Jie Zhao, Peng Xu, Xinliang Liu, Jing Yu, Wei Shangguan, Jiazhi Liu, Xiaosheng Luo, Cheng Li, Tianlei Ying, Jing Wang, Biao Yu, Ping Wang
Summary: Investigating the role of carbohydrate domains in RBD glycoproteins is crucial for the development of neutralizing antibodies and vaccines against SARS-CoV-2, but the high heterogeneity of glycoforms may result in incomplete neutralization effects. This study presents an efficient and scalable strategy for preparing six glycosylated RBDs with defined structure glycoforms, providing insights into the structure-function relationships of carbohydrates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Mojgan Atashi, Cristian D. Gutierrez Reyes, Vishal Sandilya, Waziha Purba, Parisa Ahmadi, Md. Abdul Hakim, Firas Kobeissy, Giuseppe Plazzi, Monica Moresco, Bartolo Lanuzza, Raffaele Ferri, Yehia Mechref, Mauro Fasano
Summary: This study investigates the glycoproteins in narcolepsy type 1 (NT1) disease and identifies unique N-glycopeptides that show significant changes between NT1 patients and healthy individuals. These glycopeptides may play a role in the pathophysiology of NT1.
Review
Biochemistry & Molecular Biology
Anastasia Goumenou, Nathalie Delaunay, Valerie Pichon
Summary: Glycosylation is a significant post-translational modification of proteins that can affect their basic properties, but a full characterization of glycosylation remains challenging due to sample complexity. Lectins, a group of proteins with affinity for specific sugar moieties, are commonly used for selective enrichment in affinity chromatography and solid phase extraction methods.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Biochemical Research Methods
Mona Kumari, Kishore K. R. Tetala
Summary: The review article highlights the different LC-based approaches for glycopeptide and glycoprotein enrichment published since 2016. The preparation of stationary phases, surface activation, and ligand immobilization strategies are discussed in detail. Finally, the major developments and future trends in the field are summarized.
Article
Chemistry, Multidisciplinary
Lukas Kerul, Maximilian Schrems, Alanca Schmid, Rajeshwari Meli, Christian F. W. Becker, Claudia Bello
Summary: This study describes the establishment of a semi-synthesis strategy for the preparation of modified variants of G-CSF, addressing the issues of low solubility and aggregation. The successful preparation of G-CSF variants with biological activity in cell proliferation assays was achieved.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Rebecca Notis Dardashti, Shay Laps, Jacob S. Gichtin, Norman Metanis
Summary: Human selenoprotein H, the only selenocysteine-containing protein located in the cell's nucleolus, is suggested to be involved in DNA binding, reactive oxygen species consumption, and cancer prevention. In this study, a semi-synthetic approach was used to obtain a mutated selenoprotein H and it was demonstrated to have sub-micromolar affinity for DNA binding using biolayer interferometry. The developed semi-synthetic approach can be applied for producing biologically and therapeutically relevant proteins.
Article
Oncology
Jun Li, Ting Zhao, Jing Li, Jiechen Shen, Li Jia, Bojing Zhu, Liuyi Dang, Chen Ma, Didi Liu, Fan Mu, Liangshuo Hu, Shisheng Sun
Summary: This study identified numerous unique N-glycan structures in ICC through precision N-glycoproteomic analysis, providing a valuable resource for future research on ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
MOLECULAR ONCOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Jie Zhao, Jiazhi Liu, Xinnan Liu, Qi Cao, Hongbo Zhao, Lizhen Liu, Farong Ye, Can Wang, Hong Shao, Dongxiang Xue, Houchao Tao, Bin Li, Biao Yu, Ping Wang
Summary: This article reports a highly efficient method for preparing homogeneous glycosylated IL-2 and reveals that the activity of IL-2 in activating T cell subsets is dependent on glycans, highlighting the possibility of improving current clinical medicine.
CHINESE JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Organic
Niels R. M. Reintjens, Liubov Yakovlieva, Nittert Marinus, Johan Hekelaar, Francesca Nuti, Anna Maria Papini, Martin D. Witte, Adriaan J. Minnaard, Marthe T. C. Walvoort
Summary: Selective modification of carbohydrate residues in glycopeptides is important in glycobiology. In this study, palladium-catalyzed oxidation was used to achieve the same purpose, and the catalyst proved suitable for the oxidation of glucose residues. Careful optimization of reaction conditions is necessary to achieve desired conversion rates and avoid excessive oxidation of amino acid side-chains. The resulting carbonyl function can be used for oxime-ligation with biotin.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Janelle Sauvageau, Izel Koyuturk, Frank St. Michael, Denis Brochu, Marie-France Goneau, Ian Schoenhofen, Sylvie Perret, Alexandra Star, Anna Robotham, Arsalan Haqqani, John Kelly, Michel Gilbert, Yves Durocher
Summary: Glycosylation is an important quality attribute for protein therapeutics, but current methods for monitoring glycosylation are time-consuming and difficult to analyze. In this study, researchers evaluated the use of HPAEC-PAD analysis to quickly and reliably detect glycosylation differences between protein production batches. The results were consistent with those obtained by HILIC-Fld and LC-MS.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Haoru Zhuang, Huiran Hao, Yongshun Qiu, Jinjuan Gan, Tianlu Li
Summary: Protein glycosylation is the most complex and diverse form of post-translational modification in the human body. Finding ways to improve the pharmacokinetic profile of peptide- and protein-based therapeutics, glycosylation of peptides and proteins has emerged as a promising strategy. Different synthesis strategies have attracted attention in the preparation of structurally defined glycopeptides and glycoproteins, enabling a thorough investigation of the specific effects of protein glycosylation. This review highlights recent progress in the development of novel strategies, preparation of homogeneous glycoproteins, and exploration of structure-activity relationships, while also discussing challenges and prospects.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Sunaina Kiran Prabhu, Chao Li, Guanghui Zong, Roushu Zhang, Lai-Xi Wang
Summary: Core fucosylation plays a crucial role in modulating the structure and biological functions of glycoproteins, but only a few alpha-L-fucosidases are capable of removing core fucose from intact glycoproteins. This study found that bacterial alpha-L-fucosidases from Lactobacillus casei and Bacteroides fragilis could only hydrolyze truncated Fuc alpha 1,6GlcNAc-peptide substrates, while the human alpha-L-fucosidase showed activity in removing core fucose from intact glycopeptides and glycoproteins. Additionally, the human alpha-L-fucosidase was the only enzyme that exhibited some capability to remove core fucose from intact IgG antibodies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Elany Barbosa Da Silva, Vandna Sharma, Lilian Hernandez-Alvarez, Arthur H. Tang, Alexander Stoye, Anthony J. O'Donoghue, William H. Gerwick, Richard J. Payne, James H. McKerrow, Larissa M. Podust
Summary: The potency of gallinamide A and its analogues against Trypanosoma cruzi was evaluated, and the intramolecular interactions between the aromatic substituents at the C-terminus were found to significantly contribute to the increase in anti-T. cruzi activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Angus S. Mackay, Richard J. Payne, Lara R. Malins
Summary: Electrochemical strategies for peptide and protein modification offer promising prospects for building molecular complexity, overcoming limitations of existing bioconjugation strategies, and achieving chemoselective bioconjugation chemistry.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Christopher Liczner, Cameron C. Hanna, Richard J. Payne, Christopher J. Wilds
Summary: This study presents an efficient method for synthesizing peptide-oligonucleotide conjugates using a diselenide-selenoester ligation strategy, which leads to stable amide linkages between the two biomolecules. The novel conjugation strategy increases synthesis efficiency and expands the applications of chemical modification.
Article
Rheumatology
Rochelle L. Castillo, Di Yan, Anneliese S. Ashhurst, Ashley Elliott, Maria Maddalena Angioni, Jose U. Scher, Shruti Naik, Andrea Neimainn, Scott N. Byrne, Richard J. Payne, Oliver FitzGerald, Stephen R. Pennington, Alberto Cauli, Vinod Chandran
Summary: This article summarizes the research conducted by the recipients of the 2020 GRAPPA Research Awards, presented at the 2021 GRAPPA annual meeting.
JOURNAL OF RHEUMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Ram Prasad Bhusal, Pramod Aryal, Shankar Raj Devkota, Rina Pokhrel, Menachem J. Gunzburg, Simon R. Foster, Herman D. Lim, Richard J. Payne, Matthew C. J. Wilce, Martin J. Stone
Summary: Evasin proteins in tick saliva can act as natural chemokine inhibitors, making them potential therapeutic agents for various inflammatory diseases. A structural understanding of their target selectivity is crucial for engineering evasins as targeted anti-inflammatory therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemical Research Methods
Poanna Tran, Hue N. T. Tran, Kirsten L. McMahon, Jennifer R. Deuis, Lotten Ragnarsson, Alexander Norman, Simon J. Sharpe, Richard J. Payne, Irina Vetter, Christina I. Schroeder
Summary: This study aimed to design new bivalent inhibitors of Na(V)1.7 by combining the pore blocking activity of conotoxins with the gating modifier activity of spider toxins. The potency and selectivity of the resulting bivalent toxins were evaluated by ligating a conotoxin to a spider toxin. The bivalent peptide Pro[LPATG(6)]Sx, resulting from the ligation of ProTx-II and SxIIIC, showed the best combination with conserved potency at hNa(V)1.7.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Kasuni B. Ekanayake, Mithun C. Mahawaththa, Haocheng Qianzhu, Elwy H. Abdelkader, Josemon George, Sven Ullrich, Rhys B. Murphy, Sarah E. Fry, Jason Johansen-Leete, Richard J. Payne, Christoph Nitsche, Thomas Huber, Gottfried Otting
Summary: N6-(((trimethylsilyl)-methoxy)carbonyl)-L-lysine (TMSK) and N6-trifluoroacetyl-L-lysine (TFAK) are non-canonical amino acids that can be incorporated into proteins via genetic encoding. A new aminoacyl-tRNA synthetase specific for N6-(((trimethylsilyl)methyl)-carbamoyl)-L-lysine (TMSNK) is described, which is chemically more stable than TMSK. The study demonstrates the use of these amino acids for site-specific NMR analysis of ligand binding to large proteins of limited stability and at low concentrations.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Hue N. T. Tran, Elena Budusan, Natalie J. Saez, Alexander Norman, Isaac J. Tucker, Glenn F. King, Richard J. Payne, Lachlan D. Rash, Irina Vetter, Christina I. Schroeder
Summary: Hi1a is a naturally occurring bivalent spider-venom peptide that shows promise for limiting ischemic damage. However, challenges in synthesizing and producing the peptide in large quantities have hindered progress in this area. Access to synthetic Hi1a is crucial for its development as a pharmacological tool and potential therapeutic.
Article
Multidisciplinary Sciences
Tara K. Bartolec, Xabier Vazquez-Campos, Alexander Norman, Clement Luong, Marcus Johnson, Richard J. Payne, Marc R. Wilkins, Joel P. Mackay, Jason K. K. Low
Summary: Significant advances in cryoelectron microscopy have expanded our ability to create structural models of proteins and protein complexes. Cross-linking mass spectrometry (XL-MS) is demonstrated to be a powerful tool for high-throughput experimental assessment of protein structures and interactions. The combination of XL-MS data with AlphaFold2 predictions offers opportunities to explore the structural proteome and interactome in depth.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Organic
Arthur H. Tang, Richard J. Payne
Summary: Gallinamide A, a natural product produced by cyanobacteria, shows potent anti-parasitic activity by inhibiting essential cysteine protease enzymes. It has also been found to possess strong antiviral activity against SARS-CoV-2 by covalently inhibiting the host cysteine protease cathepsin L involved in viral entry. To conduct detailed pre-clinical studies on its potential as a COVID-19 antiviral, a more efficient synthetic route was developed to obtain significant quantities of this natural product. The second generation total synthesis of Gallinamide A described here delivered the compound in a yield of 32% on a 315 mg scale over 16 steps (9 steps in the longest linear sequence).
Review
Chemistry, Multidisciplinary
Katriona Harrison, Angus S. Mackay, Lucas Kambanis, Joshua W. C. Maxwell, Richard J. Payne
Summary: The homochirality of biomolecules in nature has been crucial for the existence of life and has also provided opportunities for synthetic chemists to generate molecules with inverted chirality. Recent work on synthetic mirror-image proteins, using modern synthetic strategies, has led to their applications in protein crystallography, drug discovery, and the creation of mirror-image life.
NATURE REVIEWS CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Clara Bersi Motta Correa, Ana Carolina Kogawa, Marlus Chorilli, Herida Regina Nunes Salgado
Summary: Tyrosine sulfation is a post-translational modification that plays a crucial role in modulating the function of salivary proteins from blood feeding organisms. Utilizing synthetic chemistry, homogeneously sulfated peptides and proteins have been generated to study their structure and function. This research has provided valuable insights into the importance of tyrosine sulfate in enhancing anticoagulant activity.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Oliver H. Rathje, Lara Perryman, Richard J. Payne, Dieter W. Hamprecht
Summary: In this study, a novel approach called PROteolysis TArgeting Chimeras (PROTACs) was developed to effectively degrade MLKL and completely inhibit cell death. This work demonstrates the feasibility of targeting MLKL using a PROTAC approach and provides a powerful tool to further understand the role of MLKL within the necroptotic pathway.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Shankar Raj Devkota, Pramod Aryal, Rina Pokhrel, Wanting Jiao, Andrew Perry, Santosh Panjikar, Richard J. Payne, Matthew C. J. Wilce, Ram Prasad Bhusal, Martin J. Stone
Summary: This study focused on a type of chemokine-binding proteins called A3 evasins from tick saliva, which can bind with CC chemokines and inhibit their receptor activation. Structure-based modifications of A3 evasins can alter their chemokine selectivity, suggesting their potential applications in targeted anti-inflammatory therapy.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Kasuni B. Ekanayake, Mithun C. Mahawaththa, Haocheng Qianzhu, Elwy H. Abdelkader, Josemon George, Sven Ullrich, Rhys B. Murphy, Sarah E. Fry, Jason Johansen-Leete, Richard J. Payne, Christoph Nitsche, Thomas Huber, Gottfried Otting
Summary: TMSK, TMSNK, and TFAK are non-canonical amino acids that can be incorporated into proteins through genetic encoding. A new aminoacyl-tRNA synthetase specific for TMSNK is described, which is chemically more stable. Using the SARS-CoV-2 main protease (Mpro) as a model system, intense signals in the nuclear magnetic resonance (NMR) spectrum were observed for the trimethylsilyl and CF3 groups. The response of these groups to active-site ligands differed depending on their proximity to the active site, and the previously reported binding site of the ligand pelitinib was not confirmed.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
