Article
Chemistry, Multidisciplinary
Xiaona Li, Cristina Di Carluccio, He Miao, Lvfeng Zhang, Jintao Shang, Antonio Molinaro, Peng Xu, Alba Silipo, Biao Yu, You Yang
Summary: We report a promoter-controlled cycloglycosylation approach for the synthesis of cyclic α-(1→6)-linked mannosides up to a length of 32 units. The method relies on the role of a gold(I) complex in the proper preorganization of the ultra-large cyclic transition state. NMR experiments and a computational study revealed that the cyclic 2-mer, 4-mer, 8-mer, 16-mer, and 32-mer mannosides adopted different conformational states and shapes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Zhen Wang, Ana Gimeno, Marta G. Lete, Herman S. Overkleeft, Gijsbert A. van der Marel, Fabrizio Chiodo, Jesus Jimenez-Barbero, Jeroen D. C. Codee
Summary: We report the first total synthesis of the Streptococcus pneumoniae serotype 1 (Sp1) oligosaccharide, which is a zwitterionic capsular polysaccharide carrying unstable O-acetyl esters. The synthesis was achieved by assembling trisaccharide building blocks in a highly stereoselective manner, up to the 9-mer level. The structure investigation revealed that the oligomers adopt a right-handed helical structure, with the acetyl esters exposed on the periphery and in close proximity of the neighboring AAT residues.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Alexey G. Gerbst, Dmitry Z. Vinnitsky, Alexandra I. Tokatly, Andrey S. Dmitrenok, Vadim B. Krylov, Nadezhda E. Ustuzhanina, Nikolay E. Nifantiev
Summary: This study investigated the conformational behavior of α- and β-derivatives of glucuronic acid using NMR and quantum chemistry approaches. The introduction of sulfates had little effect on the conformation of α-linked disaccharides, while significant conformational changes were observed for β-derivatives.
Article
Chemistry, Multidisciplinary
Sooyeon Moon, Sourav Chatterjee, Peter H. Seeberger, Kerry Gilmore
Summary: By quantifying the steric and electronic contributions of all chemical reagents and solvents through quantum mechanical calculations, a random forest algorithm was trained to accurately predict the stereoselective outcome of glycosylations. The model accurately predicts stereoselectivities for unseen nucleophiles, electrophiles, acid catalyst, and solvents across a wide temperature range, and was experimentally validated on a microreactor platform. This model helps identify novel ways to control glycosylation stereoselectivity and accurately predicts previously unknown means of stereocontrol.
Article
Chemistry, Analytical
Chia Yen Liew, Hong-Sheng Luo, Ting-Yi Yang, An-Ti Hung, Bryan John Abel Magoling, Charles Pin-Kuang Lai, Chi-Kung Ni
Summary: This study re-examines high mannose N-glycans in multicellular eukaryotes using a new mass spectrometry method, and identifies many previously unreported isomers. A database is constructed for rapid identification of high mannose N-glycan isomers.
ANALYTICAL CHEMISTRY
(2023)
Article
Spectroscopy
Yugao Xu, Tingting Yang, Tao Lu, Gang Feng
Summary: The conformational equilibria of cyclohexyl isothiocyanate and its complex with water were investigated by microwave spectroscopy and theoretical calculations. The rotational spectra of the two conformers of the bare cyclohexyl isothiocyanate, a-trans and e-trans, were measured and analyzed, as well as their isotopologues. For the binary complex with water, the rotational spectra of the monohydrates of both a-trans and e-trans were measured, and water isotopologues were also observed. The noncovalent bonding features of the monohydrates were examined using natural bond orbital analysis and symmetry-adapted perturbation theory analysis.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2023)
Article
Chemistry, Organic
Catherine Alex, Alexei V. Demchenko
Summary: This paper describes a new method for the direct, highly stereoselective synthesis of glycans containing beta-linked D-mannosaminuronic acid (ManNAcA) residues, including the capsular polysaccharide of Staphylococcus aureus type 8. The method achieves stereocontrol and introduces a way to achieve complete alpha-ManNAcA stereoselectivity.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Huchen Zhang, Shijie Yi, Yuan Zhang, Zhi Hong
Summary: Asparagine-linked glycosylation (ALG, N-glycosylation) is a common protein modification in eukaryotes, and its mutation can affect the structure and localization of brassinosteroids insensitive 1 (BRI1). The removal of N-154-glycan enhances BRI1 function, while mutations on the N154 site disrupt protein folding and hydrogen bond formation. Additionally, the similarity between N154 and N275 suggests a role for N-glycans in protein conformation and intracellular localization.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Gefei Li, Yanlong Luo, Juan Mo, Masato Noguchi, Jie Jing, Zhenyang Luo, Shin-ichiro Shoda, Xin-Shan Ye
Summary: A hydrogen bond-assisted alpha-selective glycosylation reaction using DBT B-glycosyl donors was developed for constructing 1,2-cis -alpha-glycosidic bond efficiently in natural products. This method was successfully applied to directly synthesize complex oligosaccharide-derived glycolipids with simple protecting chemistry. Mechanistic studies using NMR spectroscopy and DFT calculation supported the concept of hydrogen bond-assisted glycosylation reaction for alpha-specific construction of O-glycosidic linkage.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Applied
Kameshwar Prasad, Ananay Sharma, Soumyaranjan Pati, Marc Taillefer, Florian Jaroschik, Srinivas Hotha
Summary: We report metal free conditions for the activation of alkynyl glycosyl carbonate donors using I-2/TMSOTf in stoichiometric quantities. The extrusion product was characterized as vinylidene iodide by single crystal X-ray analysis. The reaction conditions were suitable for the synthesis of various glycosides, purine/pyrimidine nucleosides, and a pentasaccharide repeating unit of Klebsiella pneumoniae (O-3 antigen).
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Helle H. Trinderup, Sofie M. Andersen, Mads Heuckendorff, Henrik H. Jensen
Summary: The study showed that increasing the concentration and amount of triflic acid catalyst can enhance beta-selectivity in the reaction, while lowering temperature has a significant effect on the glycosylation outcome. The alpha/beta-ratio in the reaction with L-menthol as glycosyl acceptor was not affected by the molecular sieve pore size or NIS activator amount.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Analytical
Yoshimi Haga, Masaki Yamada, Risa Fujii, Naomi Saichi, Takashi Yokokawa, Toshihiro Hama, Yoshihiro Hayakawa, Koji Ueda
Summary: The glycoform of therapeutic monoclonal antibodies plays a crucial role in their effectiveness, safety, and pharmacokinetics. This study developed a fast and highly sensitive analytical platform for glycan profiling using a combination of supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) and energy-resolved oxonium ion monitoring (Erexim) method. The method revealed the glycan profile characteristics and lot-to-lot heterogeneity of various therapeutic monoclonal antibodies, and detected structural variations in pharmacologically important glycan structures.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Samira Escopy, Yashapal Singh, Keith J. Stine, Alexei V. Demchenko
Summary: As the 21st century unfolds with rapid changes, new challenges have arisen in research and development. This article introduces a solution phase batch synthesis method based on the HPLC platform, which enables sequential synthesis of multiple oligosaccharides and automates the process.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Yuanyuan Bai, Xiaohong Yang, Hai Yu, Xi Chen
Summary: Innovation in process development is crucial for the industrial and laboratory production of organic compounds, such as HMOs, through biocatalysis. A substrate and process engineering strategy called MSOPME design allows for efficient synthesis of HMOs, including long-chain oligosaccharides, without the need for isolation of intermediate products. The method can be scaled up for large-scale synthesis and automation.
Article
Chemistry, Multidisciplinary
Dushen Chen, Akhilesh. K. K. Srivastava, Justyna Dubrochowska, Lin Liu, Tiehai Li, Joseph. P. P. Hoffmann, Jay. K. K. Kolls, Geert-Jan Boons
Summary: There is a pressing need for new treatment options for carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae), a common cause of life-threatening infections. In this study, a synthetic glycoconjugate vaccine was developed using oligosaccharides derived from the lipopolysaccharide of K. pneumoniae. Mice immunized with this vaccine showed a strong antibody response against K. pneumoniae.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Alena Istrate, Michael B. Geeson, Claudio D. Navo, Barbara B. Sousa, Marta C. Marques, Ross J. Taylor, Toby Journeaux, Sebastian R. Oehler, Michael R. Mortensen, Michael J. Deery, Andrew D. Bond, Francisco Corzana, Gonzalo Jimenez-Oses, Goncalo J. L. Bernardes
Summary: In this study, a new protein conjugation strategy using CPO-based reagents for selective modification of N-terminal cysteine residues was reported. The method achieved stable linkage under mild conditions and was compatible with common reducing agent DTT.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Lavinia Dunsmore, Claudio D. Navo, Julie Becher, Enrique Gil de Montes, Ana Guerreiro, Emily Hoyt, Libby Brown, Viviane Zelenay, Sigitas Mikutis, Jonathan Cooper, Isaia Barbieri, Stefanie Lawrinowitz, Elise Siouve, Esther Martin, Pedro R. Ruivo, Tiago Rodrigues, Filipa P. da Cruz, Oliver Werz, George Vassiliou, Peter Ravn, Gonzalo Jimenez-Oses, Goncalo J. L. Bernardes
Summary: This study presents a strategy to mask the redox activity of natural products containing ortho-quinones by conjugating them to a carrier. The redox-active hydroquinones can be released inside cells through a specific enzymatic trigger. Applying this strategy to antibody-mediated drug delivery, effective anticancer drugs can be obtained. This protection strategy expands the range of drugs available for next-generation targeted therapeutics.
Article
Chemistry, Multidisciplinary
Guillermo Garcia-Marquina, Judith Langer, Mercedes Sanchez-Costa, Gonzalo Jimenez-Oses, Fernando Lopez-Gallego
Summary: This study focuses on optimizing the continuous synthesis of simvastatin by immobilizing an engineered acyltransferase enzyme on controlled porous glass particles functionalized with Fe3+-catechol complexes. The immobilized enzyme showed improved thermal stability and maintained high product yield during multiple operational cycles. Under optimal flow conditions, the system achieved a 100% simvastatin yield with improved reaction mass efficiency and atom economy compared to previous studies.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2022)
Article
Chemistry, Multidisciplinary
Sara Bertuzzi, Francesca Peccati, Sonia Serna, Raik Artschwager, Simona Notova, Michel Thepaut, Gonzalo Jimenez-Oses, Franck Fieschi, Niels C. Reichardt, Jesus Jimenez-Barbero, Ana Arda
Summary: The molecular recognition features of LSECtin towards asymmetric N-glycans were scrutinized by NMR and compared to glycan microarrays. It was found that both asymmetric LDN3 and LDN6 N-glycans are recognized by LSECtin with similar affinities in solution, contrary to the results obtained on microarrays, where only LDN6 was efficiently recognized by the lectin.
ACS CENTRAL SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Lucas Schaus, Anuvab Das, Anders M. Knight, Gonzalo Jimenez-Oses, K. N. Houk, Marc Garcia-Borras, Frances H. Arnold, Xiongyi Huang
Summary: It has been discovered that an engineered protoglobin from Aeropyrnum pernix (ApePgb) can catalyze the asymmetric synthesis of trans-CF3-CPAs, with yield and enantioselectivity depending on the substrate. Computational studies show that the steric environment in the active site of the protoglobin forces iron-carbenoid and substrates to adopt a pro-cis near-attack conformation. This study demonstrates the ability of enzyme catalysts to tackle challenging chemistry problems and expands the structural diversity of CF3-CPAs for drug discovery.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Daniel Marcos-Atanes, Cristian Vidal, Claudio D. Navo, Francesca Peccati, Gonzalo Jimenez-Oses, Jose L. Mascarenas
Summary: Iridium-catalyzed borylations of aromatic C-H bonds allow for the synthesis of a wide variety of ortho-borylated derivatives. A subtle change in the bipyridine ligand, introducing a CF3 substituent at position 5, enables a complete change of regioselectivity in the borylation of aromatic amides. Computational studies suggest that this regio- and chemoselectivity is due to unusual outer-sphere interactions between the amide group of the substrate and the CF3-substituted aryl ring of the bipyridine ligand.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Marta G. Lete, Antonio Franconetti, Sara Bertuzzi, Sandra Delgado, Mikel Azkargorta, Felix Elortza, Oscar Millet, Gonzalo Jimenez-Oses, Ana Arda, Jesus Jimenez-Barbero
Summary: Fluorine (F-19) incorporation into lectins has allowed monitoring of carbohydrate binding through NMR spectroscopy. Galectin-3 (Gal3) and Galectin-8 (Gal8) with one and two carbohydrate recognition domains (CRDs), respectively, were chosen. The presence of fluorine did not significantly affect glycan binding affinity, and allowed differentiation of binding events at different sites within the same lectin.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Medicinal
Francesca Peccati, Sara Alunno-Rufini, Gonzalo Jimenez-Oses
Summary: Thermostability enhancement is crucial for the industrial and biotechnological application of biocatalysts, especially under high temperatures and harsh conditions. Predicting thermostability changes accurately is challenging due to the modifications of free energy of unfolding. In this study, we develop a new computational protocol combining global conformational sampling and energy prediction using AlphaFold and Rosetta, to quantitatively predict thermostability changes during laboratory evolution of acyltransferase LovD and lipase LipA. We demonstrate that ensembles based on AlphaFold models provide more accurate and robust thermostability predictions compared to ensembles based solely on crystallographic structures, which introduce a distortion in computed thermostabilities.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Gean M. Dal Forno, Eloah Latocheski, Ana Beatriz Machado, Julie Becher, Lavinia Dunsmore, Albert L. St John, Bruno L. Oliveira, Claudio D. Navo, Gonzalo Jimenez-Oses, Rita Fior, Josiel B. Domingos, Goncalo J. L. Bernardes
Summary: The ability to control prodrug activation by transition metals has great potential for controlled drug release in cancer cells. However, current strategies are limited to cleavage of C-O or C-N bonds, hindering the use of drugs with amino or hydroxyl groups. This study presents a palladium-mediated C-C bond cleavage method for the activation of an ortho-quinone prodrug, expanding the range of drugs that can be used.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Nuria Mazo, Imran R. Rahman, Claudio D. Navo, Jesus M. Peregrina, Jesus H. Busto, Wilfred A. . van der Donk, Gonzalo Jimenez-Oses
Summary: This study reports a common strategy for the synthesis of lanthionine derivatives using nucleophilic ring opening of cyclic sulfamidates derived from amino acids. The researchers achieved regio-, chemo-, and stereoselective intramolecular S-alkylation of a cysteine residue with N-sulfonyl sulfamidates for the synthesis of cyclic lanthionine-containing peptides. Four different analogues of cytolysin S (CylLS '') were successfully synthesized and their conformational preferences and biological activities were compared with wild-type CylLS ''.
Article
Chemistry, Multidisciplinary
Marta G. Lete, Miriam Hoffmann, Nils Schomann, Ane Martinez-Castillo, Francesca Peccati, Patrick B. Konietzny, Sandra Delgado, Nicole L. Snyder, Gonzalo Jimenez-Oses, Nicola G. A. Abrescia, Ana Arda, Laura Hartmann, Jesu's Jimenez-Barbero
Summary: Lectin-glycan interactions play a central role in various biological events. The presentation of glycans in a multivalent manner on the cell surface allows for stronger binding affinity and selectivity. In this study, the interaction of lactose-functionalized glycomacromolecules and their lipid conjugates with human galectins was investigated using NMR experiments, cryo-electron microscopy, and molecular dynamics simulations in a cell-mimicking environment.
Article
Chemistry, Multidisciplinary
Yanira Mendez, Aldrin V. Vasco, Galway Ivey, Ana Laura Dias, Peter Gierth, Barbara B. Sousa, Claudio D. Navo, Angel Torres-Mozas, Tiago Rodrigues, Gonzalo Jimenez-Oses, Goncalo J. L. Bernardes
Summary: A novel multicomponent approach combining the isonitrile-tetrazine (4+1) cycloaddition and the Ugi four-component reaction was developed to generate pyrazole amide derivatives. The scope of the reaction and the mechanistic insights of the 4H-pyrazol-4-imine tautomerization were provided. This multicomponent process expands the chemical space of pyrazole amide derivatives and offers a tool for peptide modification and stapling.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Guang Yang, Young Ju Yun, Francesca Peccati, Abdelqader M. Jamhawi, Nareshbabu Kamatham, Steffen Jockusch, Gonzalo Jimenez-Oses, A. Jean-Luc Ayitou
Summary: This study reports the synthesis and characterization of novel QDM-based chromophores that exhibit unique photo-excited behavior and aromaticity. The results show that extending the aromatic core can modulate the optoelectronic properties of these chromophores, but aromaticity imbalance in some of them leads to relative instability. Local aromaticity is identified as the main driving force for populating the excited triplet state of these chromophores.
Article
Chemistry, Organic
Marina Carranza, Ana T. Carmona, Claudio D. Navo, Inmaculada Robina, Simone Fratta, Carlos Newburn, Gonzalo Jimenez-Oses, Antonio J. Moreno-Vargas
Summary: 2-Halo-3-tosyl-oxanorbornadienes can accept two thiol molecules to form isolable oxabicyclic thiovinyl sulfones, and then react with a second thiol molecule. The substitution pattern of the oxanorbornadienic skeleton influences the reaction rate through electronic and steric factors.
Article
Chemistry, Physical
Michael Eichenberger, Thomas Schwander, Sean Hueppi, Jan Kreuzer, Peer R. E. Mittl, Francesca Peccati, Gonzalo Jimenez-Oses, Michael Naesby, Rebecca M. Buller
Summary: Anthocyanin-related glutathione transferases, traditionally known for their role in anthocyanin transport, have been found to catalyze a crucial dehydration reaction in anthocyanin synthesis. By introducing these enzymes into baker's yeast, researchers achieved a significant increase in anthocyanin production. This discovery not only sheds light on the biosynthesis of anthocyanins but also holds potential for microbial production of colorants and improvements in industrial and ornamental plant breeding.
