Article
Polymer Science
Mohammad Yasir, Andreas F. M. Kilbinger
Summary: Norbornene and cyclohexene show different polymerization behaviors using Grubbs' catalysts due to their varying ring strain energy levels; a sequence-selective cascade polymerization of a monomer containing both rings resulted in polymers with moderate molecular weight dispersities and good control over molecular weight.
Article
Chemistry, Multidisciplinary
Nils Ansmann, Thaddaus Thorwart, Lutz Greb
Summary: The Lewis superacid bis(perchlorocatecholato)silane catalyzes C-O bond metathesis of alkyl ethers with high efficiency, enabling chemoselective ring contractions of macrocyclic crown ethers and unprecedented ring-closing metathesis of polyethylene glycols for polymer-selective degradation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Dmitry S. Belov, Gabriela Tejeda, Charlene Tsay, Konstantin V. Bukhryakov
Summary: Vanadium-based catalysts have been demonstrated to catalyze ring-closing olefin metathesis reactions by well-defined V chloride alkylidene phosphine complexes, exhibiting good functional group tolerance. The properties of the imido group and phosphine were found to play a crucial role in the stability of active intermediates.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
Andrea Ojeda-Porras, Remi Aouzal, Claire Wilson, Joelle Prunet
Summary: Two synthetic routes for the ABC tricycle of Taxol are presented, both involving a relay ring-closing metathesis reaction to form the central B ring. In the first approach, the extender arm is positioned on the A ring, while the C ring bears the relay tether in the second route. Despite the efficient synthesis of metathesis precursors with diverse extender arms, the crucial metathesis reactions failed to yield the target compounds in all cases.
Article
Chemistry, Multidisciplinary
Myron Triantafyllakis, Sam Alexander, Sophie Woolford, Claire Wilson, J. Stephen Clark
Summary: The fully functionalized A-F fragment of the Pacific ciguatoxin CTX3C has been synthesized using specific reaction sequences and synthesis routes, achieving the construction of a multi-ring system and the introduction of functional groups.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Chiara Gasbarri, Serena Rosignoli, Giacomo Janson, Dalila Boi, Alessandro Paiardini
Summary: Protein-peptide interactions are crucial for cell processes and functions, and in silico predictions offer an affordable alternative to experimental methods. This study presents a new algorithm, PepThreader, for predicting and analyzing PPIs and PpIs. It achieved an accuracy of 80% on a benchmark dataset and adds to the existing tools for identifying and characterizing PPIs and PpIs.
Article
Biochemistry & Molecular Biology
Ilinka Clerc, Amin Sagar, Alessandro Barducci, Nathalie Sibille, Pau Bernado, Juan Cortes
Summary: Intrinsically disordered proteins and regions play crucial roles in biological processes by performing specialized functions related to the recognition of other biomolecules. Computational approaches have become essential tools for understanding the functional mechanisms of these proteins due to their conformational heterogeneity.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Organic
K. Prathima, D. Ashok, M. Sarasija, Ravinder Dharavath, Umesh Kumar Utkoor, V. V. S. Lakshmi, Sai Krishna Ganji, Prabhakar Sripadi
Summary: In this study, novel spiro chromanone compounds were synthesized using Ring Closing Metathesis and Cross Metathesis reactions. The spiro chromanone moiety was chosen as the core structure due to its medicinal and pharmacophoric properties. The concept of molecular hybridization was applied to successfully synthesize the target compounds.
SYNTHETIC COMMUNICATIONS
(2022)
Article
Chemistry, Applied
Gabrielle St-Pierre, Alan H. Cherney, Wencan Chen, Xiaofei Dong, Peter K. Dornan, Daniel J. Griffin, K. N. Houk, Janice B. Lin, Stephen Osgood, Maria V. Silva Elipe, Heath C. Timmons, Yong Xie, Jason S. Tedrow, Oliver R. Thiel, Austin G. Smith
Summary: AMG 176 is a drug candidate in the oncology pipeline, with Ring-closing metathesis (RCM) being a key reaction in its synthesis for constructing a 16-membered macrocycle. Process intensification was achieved through high-throughput experimentation and computational analysis, leading to significant improvements in reaction volume and yield compared to the discovery route. The RCM process developed from these studies played a crucial role in the clinical advancement of the AMG 176 program.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Chemistry, Physical
Catherine Ghosh, Biman Jana
Summary: Metal ions, especially calcium, play crucial roles in cellular functions. This study investigates how calcium affects the conformation dynamics of calmodulin and its interaction with the target protein smMLCK. The findings suggest that while calcium-independent, calcium can regulate the binding site of smMLCK peptide on calmodulin.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Chemistry, Organic
Frank Schmidt, Aparna Viswanathan Ammanath, Friedrich Goetz, Martin E. Maier
Summary: A new synthesis route was established for the macrolactone antibiotic berkeleylactone A. The synthesis involved ring-closing alkyne metathesis (RCAM) of an ester substrate with 1-propynyl termini. The carboxylic part of the substrate was assembled using alkyne chemistry, while the alcohol part of the ester was synthesized through propylene oxide opening and triple bond migration reactions. After successful RCAM, the triple bond was selectively hydrogenated and the 4,5-diol was oxidized to obtain the desired derivative. The thioether formation and reduction of the 8,9-double bond were also achieved. However, the antimicrobial activity of the analog was found to be slightly reduced.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Sambasivarao Kotha, Deepshikha Singh, Vijayalakshmi Bandi
Summary: An efficient and short synthetic sequence for highly functionalized urazole derivatives has been reported. N-substituted-1,2,4-triazoline-3,5-dione (TAD) was used as a versatile synthetic reagent. Simple reactions including allylation, ring-closing metathesis, and hydrogenation were successfully employed to construct oxygenated urazole derivatives, which may have implications in medicinal chemistry and organic synthesis.
Article
Chemistry, Medicinal
Lorenzo Calugi, Giulia Sautariello, Elena Lenci, Mauro Leucio Mattei, Crescenzo Coppa, Nicoletta Cini, Alessandro Contini, Andrea Trabocchi
Summary: The design and synthesis of peptide derivatives based on an ACE2 alpha-helix 1 epitope and subsequent stapling of the secondary structure resulted in the identification of a 9-mer peptide capable of competing with recombinant ACE2 towards Spike RBD. The cyclization method was found to better stabilize the helical structure of the peptide epitope compared to the triazole stapling via click chemistry. Molecular dynamics simulations showed that the stapled peptide not only bound to Spike RBD and sterically interfered with ACE2, but also exhibited higher affinity to the target than the parent epitope.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Xi Wang, Harry M. Greenblatt, Lavi S. Bigman, Binhan Yu, Channing C. Pletka, Yaakov Levy, Junji Iwahara
Summary: This study investigates how D/E repeats cause autoinhibition of HMGB1 and its specific binding to cisplatin-modified DNA. By varying ionic strength, the conformational equilibrium between autoinhibited and uninhibited states can be shifted, revealing fuzzy interactions of D/E repeats with other intrinsically disordered regions. Mutations mimicking post-translational modifications relevant to nuclear export of HMGB1 can moderately modulate DNA-binding affinity, possibly by impacting the autoinhibition.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Physical
Valerio Sabatino, Dario Staub, Thomas R. Ward
Summary: The synthesis of N-substituted indoles via ring-closing metathesis of indole precursors with N-terminal alkenes was reported. Good yields (up to 72%) were achieved in aqueous metathesis using commercial catalysts or artificial metalloenzymes. Furthermore, the presence of a second metathesis substrate increased the yield of N-acetylindole.
Article
Biochemistry & Molecular Biology
Yingchun Li, Lars Hemmersbach, Bernhard Krause, Nikolay Sitnikov, Anna Schlundt Nee Goederz, Diego O. Pastene Maldonado, Hans-Gunther Schmalz, Benito Yard
Summary: Over the past decade, various carbon monoxide releasing molecules (CORMs) have been developed and tested for their ability to modulate biological systems. CORMs can release CO extracellularly or intracellularly, either spontaneously or via an enzymatic trigger, with potential differences in efficacy. The spatiotemporal release of CO by CORMs plays a crucial role in their modulation of biological targets, such as HO-1 and VCAM-1 expression in cells.
Article
Chemistry, Organic
Dominik Albat, Alicia Koecher, Julia Witt, Hans-Guenther Schmalz
Summary: This study identified a new superior ligand (L24*) through screening a set of chiral phosphoramidites, which enabled the synthesis of amination products with high enantioselectivity under optimized conditions. This ligand also exhibited outstanding diastereoselectivity and negligible matched/mismatched differences in the N-allylation of other amino acid tert-butyl esters.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Alexander Belyy, Florian Lindemann, Daniel Roderer, Johanna Funk, Benjamin Bardiaux, Jonas Protze, Peter Bieling, Hartmut Oschkinat, Stefan Raunser
Summary: This study reveals in atomic detail how the TccC3 enzyme modifies actin and disrupts the cellular cytoskeleton. The binding of TccC3 to F-actin occurs through an induced-fit mechanism, leading to the transfer of ADP-ribose to a specific site on F-actin. This site-specific modification prevents the interaction of F-actin with depolymerization factors, impairing actin network turnover and promoting steady actin polymerization.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Inorganic & Nuclear
Anna Schlundt nee Goederz, Lars Hemmersbach, Steffen Romanski, Joerg-Martin Neudoerfl, Hans-Guenther Schmalz
Summary: In this research, we investigated the use of enzyme-triggered CO-releasing molecules (ET-CORMs). We were interested in modifying 2-acetoxy-5-azido-1,3-cyclohexadiene-Fe(CO)3 (rac-2) using Cu-catalyzed azide-alkyne cycloaddition (CuAAC click chemistry). Surprisingly, the treatment of [2-acetoxy-cyclohexadienyl-Fe(CO)3]+[PF6]- with certain azide compounds resulted in the formation of 2-acetoxy-1-azido-2,4-cyclohexadiene-Fe(CO)3 (rac-9) as the main product. We discovered that rac-2 is primarily formed under kinetic control and undergoes a rapid isomerization to rac-9, a thermodynamic product, through a vinylogous Winstein rearrangement mechanism. We also found that rac-9 can act as an enzyme-triggered CO-releasing molecule (ET-CORM) in the presence of porcine liver esterase.
Article
Chemistry, Organic
Joss Pepe Strache, Lukas Muenzer, Andreas Adler, Dirk Blunk, Hans-Guenther Schmalz
Summary: We investigated the enantioselective Ni-catalyzed hydrocyanation of 1,3-diarylpropenes. A series of (E)-homostilbenes were prepared by Pd-catalyzed coupling, and the hydrocyanation of various homostilbenes was studied using a Ni(cod)2/TADDOL-derived chiral phosphine-phosphite ligand catalyst system. The methodology was applied in a short synthesis of a colchicine analogue, and the absolute configuration of 2,4-diphenylbutyronitrile was determined by comparing experimental and calculated ECD spectra.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Lars Hemmersbach, Ruth Adam, Christina Plevnali, Xinmiao Zhang, Benito Yard, Hans-Gunther Schmalz
Summary: A new anti-inflammatory agent, which releases carbon monoxide (CO) and a specialized pro-resolving mediator, was successfully synthesized. It can induce HO-1 expression in endothelial cells and M2 polarized macrophages, but its role in inflammation resolution still needs to be assessed.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Lea Hartmann, Florian P. Seebeck, Hans-Guenther Schmalz, Dirk Gruendemann
Summary: Recently, a non-enzymatic multi-step cycle for the regeneration of ergothioneine (ET) has been discovered after reaction with singlet oxygen (1O2) by glutathione (GSH). Through experiments using labeled ET and high resolution mass spectrometry analysis, the reaction scheme has been revised and extended, with 1O2 attacking the imidazole ring and the sulfur of ET. The reduction of the hydroperoxide intermediates and the sulfine allows for the complete regeneration of ET by GSH, without the need for enzyme involvement.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Chemistry, Organic
Lars Hemmersbach, Hans-Guenther Schmalz
Summary: This paper presents a short and efficient synthetic access to functionalized compounds with major structural elements of the natural product populusone. By utilizing a diastereoselective Mukaiyama aldol addition and a triflic anhydride-induced oxa-Michael addition, the sensitive 2-oxa-bicyclo[2.2.2]octene unit is constructed and directly used in a subsequent Suzuki cross-coupling. Although attempts to close the strained 10-membered ring were not successful, the developed synthetic scheme allows the rapid synthesis of advanced intermediates, which may lead to the total synthesis of populusone in the future.
Article
Chemistry, Multidisciplinary
Reinhold Gregor Wuestenberg, Joerg-Martin Neudoerfl, Hans-Guenther Schmalz
Summary: Using the marine natural product ptilocaulin as a starting point, the study investigated the supramolecular behavior of N,N'-bridged guanidinium nitrates in crystalline state. Various N,N'-bridged guanidines were synthesized and converted into nitrate salts, and their crystal structures were determined. The study identified several recurring supramolecular motifs formed by charge-assisted self-assembly and revealed the value of N,N'-bridged guanidines as building blocks for supramolecular chemistry and crystal engineering.
ISRAEL JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Organic
Lukas Muenzer, Hans-Guenther Schmalz
Summary: In this paper, the results and experience gained from 20 years of research in the field of polyketidic natural products with a tetra-ortho-substituted benzophenone substructure are summarized. Despite the challenges posed by the intense interactions of the functional groups adjacent to the ketone bridge, the synthesis of such systems is important for understanding the non-enzymatic formation of related compounds in Nature. Successes, failures, and surprising reactivities are reported based on the approaches used to target Mumbaistatin and Pestalone, both of which are of high biological relevance.
Article
Chemistry, Organic
Dominik Albat, Slim Chiha, Stephan Dohmen, Pascal M. Engelhardt, Hanna Sebode, Arne Soicke, Matthias Barone, Matthias Mueller, Ronald Kuehne, Hans-Guenther Schmalz
Summary: In this study, we describe the modular assembly of ProM-based pentapeptidic EVH1 ligands through liquid phase peptide synthesis, which allows for facile alteration of the C-terminal ProM unit and improved overall yields and purity.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Iuliia A. A. Gracheva, Hans-Gunther Schmalz, Elena V. V. Svirshchevskaya, Ekaterina S. S. Shchegravina, Alexey Yu. Fedorov
Summary: We developed a four-step semisynthetic approach to obtain a highly versatile allocolchicine-related chiral aryne intermediate from natural colchicine. The generated benzyne intermediate produced a range of non-racemic heterocyclic allocolchicinoids, which exhibited potent cytotoxicity against COLO 357, OSA, and Raji cells. This methodology is attractive for the synthesis of new libraries of cytotoxic tubulin inhibitors.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Chuanke Chong, Le Chang, Isabelle Grimm, Qunlong Zhang, Yang Kuang, Bingjian Wang, Jingyi Kang, Wenhui Liu, Julian Baars, Yuanqiang Guo, Hans-Guenther Schmalz, Zhaoyong Lu
Summary: We present a concise and diverse synthetic strategy for the revised structures of marine anti-cancer sesquiterpene hydroquinone meroterpenoids (+)-dysiherbols A-E (6-10). The total synthesis was accomplished using dimethyl predysiherbol 14 as a key intermediate. Two different improved syntheses of dimethyl predysiherbol 14 were developed, and two different approaches were used to construct the core ring system. The total synthesis of (+)-dysiherbols A-E (6-10) was achieved by starting from dimethyl predysiherbol 14, leading to the revision of their originally proposed structures.
Article
Chemistry, Organic
Marco T. Klein, Bernhard M. Krause, Jorg-Martin Neudorfl, Ronald Kuhne, Hans-Gunther Schmalz
Summary: A synthesis method for the new tetracyclic scaffold ProM-19 involves preparing key building blocks through specific reactions and synthesizing the target compound. This synthesis method was also applied for the preparation of a potential ligand.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Liliane Abodo Onambele, Natalie Hoffmann, Lisa Kater, Lars Hemmersbach, Jorg-Martin Neudorfl, Nikolay Sitnikov, Benjamin Kater, Corazon Frias, Hans-Gunther Schmalz, Aram Prokop
Summary: Hexacarbonyl[1,3-dimethoxy-5-((4 '-methoxyphenyl)ethynyl)benzene]dicobalt (NAHO27), an organometallic analogue of combretastatin A-4, has shown specific apoptotic activity against lymphoma and leukemia cells, including drug-resistant cells, through the mitochondrial pathway. Mechanistic investigations revealed the involvement of caspases, Bcl-2, smac/DIABLO, and mitochondrial membrane potential change. This compound can be a potential therapeutic agent for cancer treatment.
RSC MEDICINAL CHEMISTRY
(2022)
