Article
Chemistry, Multidisciplinary
Mohadeseh Dastpeyman, John A. Karas, Azin Amin, Bradley J. Turner, Fazel Shabanpoor
Summary: Cell penetrating peptides (CPPs) are efficient vectors for intracellular delivery of biologically active agents like therapeutic antisense oligonucleotides (ASOs). Conjugating ASOs to CPPs through native chemical ligation (NCL) significantly improves their cellular permeability and therapeutic efficacy. This study demonstrates that chemo-selective NCL is a superior strategy for synthesizing bi-/trifunctional CPP-ASO conjugates with high efficiency.
FRONTIERS IN CHEMISTRY
(2021)
Article
Chemistry, Organic
Nathalie Ollivier, Eliott Roy, Vangelis Agouridas, Vincent Diemer, Oleg Melnyk
Summary: 4-Mercaptophenylacetic acid (MPAA) is a commonly used catalyst for native chemical ligation (NCL), but it requires a large excess for practical rates (up to 50-100 equivalents). In this study, we found that the catalytic potency of MPAA can be enhanced by introducing a stretch of arginines in the departing thiol of the thioester. This electrostatically assisted NCL reaction allows for rapid synthesis using substoichiometric concentrations of MPAA, which is advantageous for practical applications.
Article
Chemistry, Multidisciplinary
Sebastian Trunschke, Emanuele Piemontese, Olaf Fuchs, Skander Abboud, Oliver Seitz
Summary: By introducing new ligation auxiliaries, this study expands the applicability of native chemical ligation and investigates the role of the pyridine-ring nitrogen in the auxiliaries. The study successfully synthesizes peptides with special structures, demonstrating that the new auxiliary has increased stability and wide application potential.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Evelyn M. Molloy, Maria Dell, Veit G. Haensch, Kyle L. Dunbar, Romy Feldmann, Ansgar Oberheide, Lydia Seyfarth, Jana Kumpfmueller, Therese Horch, Hans-Dieter Arndt, Christian Hertweck
Summary: This study reports the discovery of a genuine chemical mediator, homodetic cyclopeptide (cAIP), that controls endospore formation in clostridia, and reveals a widespread feature of clostridial AIP biosynthesis, namely the novel enzyme-primed, intramolecular native chemical ligation (NCL).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Nikolaos Kaplaneris, Alejandro Puet, Felix Kallert, Julia Poehlmann, Lutz Ackermann
Summary: We achieved the late-stage diversification of structurally complex peptides through palladium-catalyzed C-H arylation. The tunability and ease of preparation of arylthianthrenium salts allowed us to forge sterically congested biaryl linkages between tryptophan-containing peptides and drug, natural product, and peptidic scaffolds. The robustness of the palladium catalysis regime was demonstrated by the full tolerance of sensitive and coordinating functional groups. As a result, we efficiently accessed highly decorated, labelled, conjugated, and ligated linear and cyclic peptides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Dipankar Chaudhuri, Rajasekaran Ganesan, Alicia Vogelaar, Mansour A. Dughbaj, Paul M. Beringer, Julio A. Camarero
Summary: A new epimerization-free approach for the Fmoc-based synthesis of murepavadin using intramolecular native chemical ligation and desulfurization reaction has been developed, resulting in a high yield of bioactive murepavadin in two steps. The synthetic peptide antibiotic showed potent activity against different clinical isolates of P. aeruginosa. This approach can be easily adapted for the production of murepavadin analogues and other backbone-cyclized peptides.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Cheng-Ting Shih, Bo-Hong Kuo, Chun-Yi Tsai, Mei-Chun Tseng, Jiun-Jie Shie
Summary: This study demonstrates that dibenzocyclooctendiones (DBCDOs) are efficient chemical reagents for the site-specific labeling of arginine-containing biomolecules. DBCDOs undergo an irreversible ring-contracted rearrangement with the guanidinium group on arginine residues under mild reaction conditions, resulting in regioselective dual-labeled arginine residues.
Article
Polymer Science
Subhajit Pal, Ankita Mandal, Linda Hong, Roberto D. Ortuso, Alke Petri-Fink, Stefan Salentinig, Andreas F. M. Kilbinger
Summary: Native chemical ligation (NCL) is an excellent and efficient method for the chemical synthesis of proteins and peptides from unprotected short peptide fragments. It offers high chemo- and regioselectivity, allowing the synthesis of functional biomacromolecules without protection-deprotection strategies under mild conditions. In this study, the potential of NCL for non-natural polymer conjugation was explored, and diblock and ABA triblock copolymers were synthesized with high efficiency. The successful synthesis of non-natural polymers using NCL was confirmed by size exclusion chromatography and NMR spectroscopy analysis.
Article
Chemistry, Multidisciplinary
Luisa Maria Gatzemeier, Franc Meyer, Ulf Diederichsen, Tiago Fleming Outeiro
Summary: Alpha-Synuclein is a protein involved in neurodegenerative disorders that accumulate in brain protein inclusions. We have developed a chemical synthesis method for Alpha-Synuclein, allowing the synthesis of protein variants for further investigation of its structure and aggregation behavior.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Olaf Fuchs, Sebastian Trunschke, Hendrik Hanebrink, Marc Reimann, Oliver Seitz
Summary: This study introduces a new auxiliary, MPyE, designed to catalyze ligation reactions in chemical protein synthesis. The MPyE auxiliary proves to be effective in providing useful rates even for junctions containing proline or a beta-branched amino acid.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Wei-Wei Shi, Chaowei Shi, Tong-Yue Wang, Yu-Lei Li, Yong-Kang Zhou, Xu-Han Zhang, Donald Bierer, Ji-Shen Zheng, Lei Liu
Summary: The chemical synthesis of correctly folded proteins with multiple or interchain disulfide bonds was expedited using a removable glycosylation modification (RGM) strategy, which introduces O-linked beta-N-acetylglucosamine (O-GlcNAc) groups to improve folding and can be efficiently removed afterwards.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Austin D. Marchese, Andrew G. Durant, Mark Lautens
Summary: A simple and modular approach using palladium catalysis to synthesize bis-heterocyclic spirocycles is reported. The method leverages a Mizoroki-Heck-type reaction to generate neopentylpalladium species, allowing for intramolecular C-H activation on a wide array of C-H bonds to produce a variety of spirocycles. The reaction is scalable, allowing for easy incorporation of biologically relevant heterocycles without the need for flash column chromatography.
Article
Chemistry, Organic
Jie Zhao, Jiazhi Liu, Xinliang Liu, Farong Ye, Siyao Wang, Ping Wang
Summary: IL-1 alpha was semi-synthesized using expressed threonine ligation and native chemical ligation-desulfurization. This method can be applied to the synthesis of other Cys-free glycoproteins.
TETRAHEDRON LETTERS
(2022)
Article
Chemistry, Organic
Avijit K. Adak, Yung-Yu Su, Wei-Hao Wang, Chin-Lan Lin, Hao Gu, Yi-Chen Huang, Zhe-Jie Zhang, Chai-Lin Kao, Chun-Cheng Lin
Summary: Photoactivatable ligation auxiliaries simplify protein assembly by cleaving the auxiliary after ligation through photolysis. This study introduces an easy-to-attach TmNpE-auxiliary at the internal side-chain of N-terminal peptide fragments, enabling long-range ligation and photolytic removal in an aqueous buffer. The method's versatility is demonstrated by synthesizing a hPD-L1 peptide inhibitor. The TmNpE group offers easy introduction, compatibility with peptide ligation reactions, and mild cleavage conditions.
Article
Chemistry, Multidisciplinary
Skander A. Abboud, El Hadji Cisse, Michel Doudeau, Helene Benedetti, Vincent Aucagne
Summary: One of the main limitations in the chemical synthesis of proteins through NCL is the limited solubility of some peptide segments. A common solution is to derivatize the segment with a temporary solubilizing tag, which can be introduced on the thioester segment and removed concomitantly with the NCL reaction. This approach has been generalized to N-terminal cysteinyl segment counterparts and can be easily automated.
Article
Polymer Science
Brigitte A. G. Lamers, Brett P. P. Fors, E. W. Meijer
Summary: The effect of blending oligomers of different lengths of discrete hydrazone end-functionalized oligo(dimethylsiloxanes) on morphological order was studied. A distinct boundary exists between good and poor morphological order at a certain dispersity.
JOURNAL OF POLYMER SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Joost J. B. van der Tol, Tom A. P. Engels, Ruth Cardinaels, Ghislaine Vantomme, E. W. Meijer, Fabian Eisenreich
Summary: Reported a method for light-controlled liquid-to-solid transition of polysiloxanes, which forms strong supramolecular cross-links through photoisomerization. This method allows for tailoring the mechanical properties of polymers without the use of plasticizers or hardeners.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Martin H. C. van Son, Anton M. Berghuis, Bas F. M. de Waal, Felix A. Wenzel, Klaus Kreger, Hans-Werner Schmidt, Jaime Gomez Rivas, Ghislaine Vantomme, E. W. Meijer
Summary: In this study, functionalization of C-3-symmetric carbonyl-bridged triarylamine trisamide (CBT) with oligodimethylsiloxane (oDMS) side chains was shown to lead to fully covered surfaces with aligned domains, enabling long-range exciton transport.
ADVANCED MATERIALS
(2023)
Article
Mechanics
Emmanouil Vereroudakis, Nathan Van Zee, E. W. Meijer, Dimitris Vlassopoulos
Summary: We investigated the behavior of a supramolecular polymer under repeated shear-startup runs. This test, proposed 50 years ago, is used to measure disentanglement kinetics in linear polymers. The recovery time was found to mainly reflect chain reorientation, but for the supramolecular polymer in this study, it was rate independent. This difference is attributed to the different mechanism of stress relaxation involving bond breaking/recombination and reptation processes. The repeated shear-startup protocol can serve as an indicator of polymer signatures and a tool to evaluate stress relaxation models.
JOURNAL OF NON-NEWTONIAN FLUID MECHANICS
(2023)
Article
Chemistry, Multidisciplinary
Stef A. H. Jansen, Elisabeth Weyandt, Tsubasa Aoki, Takayoshi Akiyama, Yoshimitsu Itoh, Ghislaine Vantomme, Takuzo Aida, E. W. Meijer
Summary: Complexity in supramolecular polymer systems is caused by interactions between different components, including solvent molecules. This study reveals that both thermally bisignate and dilution-induced assembly phenomena in multicomponent systems are driven by the same underlying interaction mechanism. By investigating the interaction between amide-decorated supramolecular polymers and aliphatic alcohols, the temperature-dependency and dominance of the interaction at high monomer concentrations were unveiled. These insights allow for the control and manipulation of supramolecular polymer systems, opening the door to building complex and functional structures.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Correction
Chemistry, Multidisciplinary
Alexander R. Epstein, Jeremy Demarteau, Brett A. Helms, Kristin A. Persson
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Alexander R. Epstein, Jeremy Demarteau, Brett A. Helms, Kristin A. Persson
Summary: The design of circular polymers is necessary due to the lack of efficient recycling methods for many commodity plastics. Polydiketoenamines (PDKs) stand out for their ability to undergo selective depolymerization in strong acid, allowing monomers to be recovered. The chemistry of the cross-linker, far from the reaction center, has been found to affect the depolymerization rate of PDKs, with a proximal amine in the cross-linker significantly accelerating the process.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Yingluo Zhao, Hiroko Kawano, Hiroshi Yamagishi, Saya Otake, Yoshimitsu Itoh, Hubiao Huang, E. W. Meijer, Takuzo Aida
Summary: In this article, we report the complex pathway complexity in thesupramolecular polymerization of a chiral monomer, which exhibits an anomalous chiroptical feature. Through AgBF4-mediated supramolecular polymerization, we developed a planar-chiral ferrocene-cored tetratopic pyridyl monomer FcL, leading to the formation of nanotubes composed of metal-organic nanorings (FcNTs). The formation of homochiral nanorings (FcNRs) was observed even from racemic FcL, suggesting the existence of two competing pathways for producing FcNRs in the polymerization process.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Freek V. de Graaf, Stef A. H. Jansen, Tobias Schnitzer, E. W. Meijer, Ghislaine Vantomme
Summary: Amplification of asymmetry in complex molecular systems is achieved by controlling the helicity of supramolecular assemblies through non-stereoselective methylation reactions. Methylating chiral glutamic acid side chains in benzene-1,3,5-tricarboxamide (BTA) derivatives modulates the assembly properties. The introduction of methyl ester-BTAs as reacted comonomers induces a stronger bias in the screw-sense of helical fibers predominantly composed of stacked achiral alkyl-BTA monomers, leading to asymmetry amplification.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Laura Rijns, Joris W. Peeters, Simone I. S. Hendrikse, Marle E. J. Vleugels, Xianwen Lou, Henk M. Janssen, E. W. Meijer, Patricia Y. W. Dankers
Summary: This research reveals the importance of molecular dynamics and gel dynamics in cellular spreading. Epithelial cells are insensitive to gel dynamics, while fibroblasts are sensitive to the gel dynamics in soft gels and dependence on gel stiffness.
CHEMISTRY OF MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Stef A. H. Jansen, Hao Su, Tobias Schnitzer, Ghislaine Vantomme, E. W. Meijer
Summary: In this study, the temperature-dependent microstructure of copolymers of triazine- and benzene-derivatives was investigated. It was found that the interplay between these two monomers determines the helicity of the copolymers, similar to the mixed majority-rules phenomenon.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Jake X. Shi, Nicodemo R. Ciccia, Subhajit Pal, Diane D. Kim, John N. Brunn, Carlos Lizandara-Pueyo, Martin Ernst, Alexander M. Haydl, Phillip B. Messersmith, Brett A. Helms, John F. Hartwig
Summary: In this study, strategies for derivatizing oxidized polyethylene with functional groups were described. The presence of ketones and alcohols in the polyethylene were controlled through different catalytic reactions. The introduction of esters and oximes onto the polymer improved its surface and bulk properties. The functionalized polymers were separated from plastic blends through selective dissolution, demonstrating the potential for novel approaches in polymer separation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Wenhao Zhang, Ryan Walser-Kuntz, Jacob S. Tracy, Tim K. Schramm, James Shee, Martin Head-Gordon, Gan Chen, Brett A. Helms, Melanie S. Sanford, F. Dean Toste
Summary: Redox flow batteries (RFBs) are a promising technology for energy storage. This study introduces a new organic scaffold, indolo[2,3-b]quinoxaline, as a stable and high-performance anolyte for nonaqueous RFBs. When paired with MEEPT, it achieves a 2.3 V all-organic RFB.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Joost J. B. van der Tol, Ghislaine Vantomme, E. W. Meijer
Summary: In this study, the compatibility between solvents and supramolecular polymers was systematically investigated using Hansen solubility parameters (δ (D), δ (H), and δ (P)). A dual-sphere model was applied to describe the solubility space of the monomeric state and supramolecular polymer state. Further studies revealed the formation of higher-order aggregated structures due to subtle differences in solvent polarity. The model was also applied to structurally different monomers, demonstrating its generality and the importance of supramolecular monomer design.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Jiwoong Bae, Zhuoying Zhu, Jiajun Yan, Dong-Min Kim, Youngmin Ko, Anubhav Jain, Brett A. Helms
Summary: We designed supramolecular organo-ionic (ORION) electrolytes to separate the cathode and solid-electrolyte particles in solid-state batteries (SSBs) and enable the recycling of cathodes from the recovered materials. SSBs implementing ORION electrolytes showed less than 20% capacity fade after hundreds of cycles at 45 degrees C. Refurbished cells using a low-temperature solvent process recovered 90% of their initial capacity and sustained it for an additional 100 cycles with 84% capacity retention in their second life.
