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Publikation Modified oligonucleotides(World Intellectual Property Organization, 08.01.1998) De Mesmaeker, Alain; Wendeborn, Sebastian; Lebreton, JaquesIt is one object of the present invention to provide an oligonucleotide of formula (1): 5'-(U)n-3' in which U is an identical or different radical of a natural or a synthetic nucleoside, wherein the oligonucleotide comprises at least one modified nucleotide dimer comprising two nucleoside analogs connected via an amide-bond that has a certain configuration; the synthesis of these compounds and their use in pharmaceutical preparations.12 - PatentPublikation Dynemicin analogs: Syntheses, methods of preparation and use(United States Patent and Trademark Office, 04.01.1994) Smith, Adrian L.; Hwang, Chan-Kou; Wendeborn, Sebastian; Nicolaou, Kyriacos C.; Schreiner, Erwin P.; Stahl, Wilhelm; Dai, Wei-Min; Maligres, Peter E.; Suzuki, ToshioA fused ring system compound is disclosed that contains an epoxide group on one side or the fused rings and an enediyne macrocyclic ring on the other side of the fused rings. The compounds have DNA-cleaving, antimicrobial and tumor growth-inhibiting properties. Chimeric compounds having the fused ring system compound as an aglycone bounded to (i) a sugar moiety as the ogligosaccharide portion or(ii) a monoclonal antibody or antibody combining site portion thereof that immunoreacts with target tumor cells are also disclosed. Compositions containing a compound or a chimer are disclosed, as are methods or preparing a compound.12 - PatentPublikation Enantiomeric dynemicin analogs, preparation and use thereof(World Intellectual Property Organization, 25.11.1993) Smith, Adrian L.; Wendeborn, Sebastian; Nicolaou, Kyriacos; Schreiner, Erwin P.; Dai, Wei-Min; Susuki, ToshioAn enantiomer of a fused ring system compound is disclosed that contains an epoxide group on one side of the fused rings and an enediyne macrocyclic ring on the other side of the fused rings. The enantiomeric compounds have DNA-cleaving, antimicrobial and tumor growth-inhibiting properties that are enhanced over their racemates. Chimeric compounds having the enantiomeric fused ring system compound as an aglycone bonded to (i) a sugar moiety as the oligosaccharide portion or (ii) a monoclonal antibody or antibody combining site portion thereof that immunoreacts with target tumor cells are also disclosed. Compositions containing an enatiomeric compound or an enantiomeric chimer are disclosed, as are methods of preparing an enantiomeric compound.12 - PatentPublikation Computationally driven discovery of SARS-CoV-2 Mpro inhibitors. From design to experimental validation(Royal Society of Chemistry, 01.01.2022) El Khoury, Léa; Jing, Zhifeng; Cuzzolin, Alberto; Deplano, Alessandro; Loco, Daniele; Sattarov, Boris; Hédin, Florent; Ho, Chris; El Ahdab, Dina; Jaffrelot Inizan, Theo; Sturlese, Mattia; Sosic, Alice; Volpiana, Martina; Lugato, Angela; Barone, Marco; Gatto, Barbara; Macchia, Maria Ludovica; Bellanda, Massimo; Battistutta, Roberto; Salata, Cristiano; Kondratov, Ivan; Iminov, Rustam; Khairulin, Andrii; Mykhalonok, Yaroslav; Pochepko, Anton; Chashka-Ratushnyi, Volodymyr; Kos, Iaroslava; Moro, Stefano; Montes, Matthieu; Ren, Pengyu; Ponder, Jay W.; Lagardère, Louis; Piquemal, Jean-Philip; Sabbadin, Davide; Wendeborn, SebastianWe report a fast-track computationally driven discovery of new SARS-CoV-2 main protease (Mpro) inhibitors whose potency ranges from mM for the initial non-covalent ligands to sub-μM for the final covalent compound (IC50 = 830 ± 50 nM). The project extensively relied on high-resolution all-atom molecular dynamics simulations and absolute binding free energy calculations performed using the polarizable AMOEBA force field. The study is complemented by extensive adaptive sampling simulations that are used to rationalize the different ligand binding poses through the explicit reconstruction of the ligand–protein conformation space. Machine learning predictions are also performed to predict selected compound properties. While simulations extensively use high performance computing to strongly reduce the time-to-solution, they were systematically coupled to nuclear magnetic resonance experiments to drive synthesis and for in vitro characterization of compounds. Such a study highlights the power of in silico strategies that rely on structure-based approaches for drug design and allows the protein conformational multiplicity problem to be addressed. The proposed fluorinated tetrahydroquinolines open routes for further optimization of Mpro inhibitors towards low nM affinities.01A - Beitrag in wissenschaftlicher Zeitschrift