TY - GEN A1 - Bourgat, Yannick A1 - Tiersch, Brigitte A1 - Koetz, Joachim A1 - Menzel, Henning T1 - Enzyme degradable polymersomes from chitosan-g-[poly-l-lysine-block-epsilon-caprolactone] copolymer T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - The scope of this study includes the synthesis of chitosan-g-[peptide-poly-epsilon-caprolactone] and its self-assembly into polymeric vesicles employing the solvent shift method. In this way, well-defined core-shell structures suitable for encapsulation of drugs are generated. The hydrophobic polycaprolactone side-chain and the hydrophilic chitosan backbone are linked via an enzyme-cleavable peptide. The synthetic route involves the functionalization of chitosan with maleimide groups and the preparation of polycaprolactone with alkyne end-groups. A peptide functionalized with a thiol group on one side and an azide group on the other side is prepared. Thiol-ene click-chemistry and azide-alkyne Huisgen cycloaddition are then used to link the chitosan and poly-epsilon-caprolactone chains, respectively, with this peptide. For a preliminary study, poly-l-lysin is a readily available and cleavable peptide that is introduced to investigate the feasibility of the system. The size and shape of the polymersomes are studied by dynamic light scattering and cryo-scanning electron microscopy. Furthermore, degradability is studied by incubating the polymersomes with two enzymes, trypsin and chitosanase. A dispersion of polymersomes is used to coat titanium plates and to further test the stability against enzymatic degradation. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1382 KW - chitosan KW - click chemistry KW - drug delivery system KW - enzyme KW - polymersomes KW - poly‐ ε ‐ caprolactone Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-566584 SN - 1866-8372 IS - 1 ER - TY - JOUR A1 - Solger, Franziska A1 - Kunz, Tobias C. A1 - Fink, Julian A1 - Paprotka, Kerstin A1 - Pfister, Pauline A1 - Hagen, Franziska A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Seibel, Jürgen A1 - Rudel, Thomas T1 - A role of sphingosine in the intracellular survival of Neisseria gonorrhoeae JF - Frontiers in Cellular and Infection Microbiology N2 - Obligate human pathogenic Neisseria gonorrhoeae are the second most frequent bacterial cause of sexually transmitted diseases. These bacteria invade different mucosal tissues and occasionally disseminate into the bloodstream. Invasion into epithelial cells requires the activation of host cell receptors by the formation of ceramide-rich platforms. Here, we investigated the role of sphingosine in the invasion and intracellular survival of gonococci. Sphingosine exhibited an anti-gonococcal activity in vitro. We used specific sphingosine analogs and click chemistry to visualize sphingosine in infected cells. Sphingosine localized to the membrane of intracellular gonococci. Inhibitor studies and the application of a sphingosine derivative indicated that increased sphingosine levels reduced the intracellular survival of gonococci. We demonstrate here, that sphingosine can target intracellular bacteria and may therefore exert a direct bactericidal effect inside cells. KW - Neisseria gonorrhoeae KW - sphingosine KW - sphingolipids KW - sphingosine kinases KW - invasion KW - survival KW - click chemistry Y1 - 2020 U6 - https://doi.org/10.3389/fcimb.2020.00215 SN - 2235-2988 VL - 10 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Keckeis, Philipp A1 - Zeller, Enriko A1 - Jung, Carina A1 - Besirske, Patricia A1 - Kirner, Felizitas A1 - Ruiz-Agudo, Cristina A1 - Schlaad, Helmut A1 - Cölfen, Helmut T1 - Modular toolkit of multifunctional block copoly(2-oxazoline)s for the synthesis of nanoparticles JF - Chemistry - a European journal N2 - Post-polymerization modification provides an elegant way to introduce chemical functionalities onto macromolecules to produce tailor-made materials with superior properties. This concept was adapted to well-defined block copolymers of the poly(2-oxazoline) family and demonstrated the large potential of these macromolecules as universal toolkit for numerous applications. Triblock copolymers with separated water-soluble, alkyne- and alkene-containing segments were synthesized and orthogonally modified with various low-molecular weight functional molecules by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and thiol-ene (TE) click reactions, respectively. Representative toolkit polymers were used for the synthesis of gold, iron oxide and silica nanoparticles. KW - block copolymers KW - click chemistry KW - nanoparticles KW - ring-opening KW - polymerization KW - surfactants Y1 - 2021 U6 - https://doi.org/10.1002/chem.202101327 SN - 0947-6539 SN - 1521-3765 VL - 27 IS - 32 SP - 8283 EP - 8287 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Bourgat, Yannick A1 - Tiersch, Brigitte A1 - Koetz, Joachim A1 - Menzel, Henning T1 - Enzyme degradable polymersomes from chitosan-g-[poly-l-lysine-block-epsilon-caprolactone] copolymer JF - Macromolecular bioscience N2 - The scope of this study includes the synthesis of chitosan-g-[peptide-poly-epsilon-caprolactone] and its self-assembly into polymeric vesicles employing the solvent shift method. In this way, well-defined core-shell structures suitable for encapsulation of drugs are generated. The hydrophobic polycaprolactone side-chain and the hydrophilic chitosan backbone are linked via an enzyme-cleavable peptide. The synthetic route involves the functionalization of chitosan with maleimide groups and the preparation of polycaprolactone with alkyne end-groups. A peptide functionalized with a thiol group on one side and an azide group on the other side is prepared. Thiol-ene click-chemistry and azide-alkyne Huisgen cycloaddition are then used to link the chitosan and poly-epsilon-caprolactone chains, respectively, with this peptide. For a preliminary study, poly-l-lysin is a readily available and cleavable peptide that is introduced to investigate the feasibility of the system. The size and shape of the polymersomes are studied by dynamic light scattering and cryo-scanning electron microscopy. Furthermore, degradability is studied by incubating the polymersomes with two enzymes, trypsin and chitosanase. A dispersion of polymersomes is used to coat titanium plates and to further test the stability against enzymatic degradation. KW - chitosan KW - click chemistry KW - drug delivery system KW - enzyme KW - polymersomes KW - poly‐ ε ‐ caprolactone Y1 - 2020 U6 - https://doi.org/10.1002/mabi.202000259 SN - 1616-5187 SN - 1616-5195 VL - 21 IS - 1 SP - 1 EP - 9 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Dey, Pradip A1 - Bergmann, Tobias A1 - Cuellar-Camacho, Jose Luis A1 - Ehrmann, Svenja A1 - Chowdhury, Mohammad Suman A1 - Zhang, Minze A1 - Dahmani, Ismail A1 - Haag, Rainer A1 - Azad, Walid T1 - Multivalent flexible nanogels exhibit broad-spectrum antiviral activity by blocking virus entry JF - ACS nano N2 - The entry process of viruses into host cells is complex and involves stable but transient multivalent interactions with different cell surface receptors. The initial contact of several viruses begins with attachment to heparan sulfate (HS) proteoglycans on the cell surface, which results in a cascade of events that end up with virus entry. The development of antiviral agents based on multivalent interactions to shield virus particles and block initial interactions with cellular receptors has attracted attention in antiviral research. Here, we designed nanogels with different degrees of flexibility based on dendritic polyglycerol sulfate to mimic cellular HS. The designed nanogels are nontoxic and broad-spectrum, can multivalently interact with viral glycoproteins, shield virus surfaces, and efficiently block infection. We also visualized virus-nanogel interactions as well as the uptake of nanogels by the cells through clathrin-mediated endocytosis using confocal microscopy. As many human viruses attach to the cells through HS moieties, we introduce our flexible nanogels as robust inhibitors for these viruses. KW - multivalent KW - herpes simplex virus KW - heparan sulfate KW - nanoparticles KW - click chemistry KW - polyglycerol Y1 - 2018 U6 - https://doi.org/10.1021/acsnano.8b01616 SN - 1936-0851 SN - 1936-086X VL - 12 IS - 7 SP - 6429 EP - 6442 PB - American Chemical Society CY - Washington ER - TY - THES A1 - Zemella, Anne T1 - Fluoreszenzmarkierung und Modifizierung von komplexen Proteinen in eukaryotischen zellfreien Systemen durch die Etablierung von orthogonalen tRNA/Aminoacyl-tRNA-Synthetase-Paaren T1 - Fluorescent labeling and modification of complex proteins in eukaryotic cell-free systems by establishing orthogonal tRNA/aminoacyl-tRNA-synthetase pairs N2 - Die funktionelle Charakterisierung von therapeutisch relevanten Proteinen kann bereits durch die Bereitstellung des Zielproteins in adäquaten Mengen limitierend sein. Dies trifft besonders auf Membranproteine zu, die aufgrund von zytotoxischen Effekten auf die Produktionszelllinie und der Tendenz Aggregate zu bilden, in niedrigen Ausbeuten an aktivem Protein resultieren können. Der lebende Organismus kann durch die Verwendung von translationsaktiven Zelllysaten umgangen werden- die Grundlage der zellfreien Proteinsynthese. Zu Beginn der Arbeit wurde die ATP-abhängige Translation eines Lysates auf der Basis von kultivierten Insektenzellen (Sf21) analysiert. Für diesen Zweck wurde ein ATP-bindendes Aptamer eingesetzt, durch welches die Translation der Nanoluziferase reguliert werden konnte. Durch die dargestellte Applizierung von Aptameren, könnten diese zukünftig in zellfreien Systemen für die Visualisierung der Transkription und Translation eingesetzt werden, wodurch zum Beispiel komplexe Prozesse validiert werden können. Neben der reinen Proteinherstellung können Faktoren wie posttranslationale Modifikationen sowie eine Integration in eine lipidische Membran essentiell für die Funktionalität des Membranproteins sein. Im zweiten Abschnitt konnte, im zellfreien Sf21-System, für den G-Protein-gekoppelten Rezeptor Endothelin B sowohl eine Integration in die endogen vorhandenen Endoplasmatisch Retikulum-basierten Membranstrukturen als auch Glykosylierungen, identifiziert werden. Auf der Grundlage der erfolgreichen Synthese des ET-B-Rezeptors wurden verschiedene Methoden zur Fluoreszenzmarkierung des Adenosin-Rezeptors A2a (Adora2a) angewandt und optimiert. Im dritten Abschnitt wurde der Adora2a mit Hilfe einer vorbeladenen tRNA, welche an eine fluoreszierende Aminosäure gekoppelt war, im zellfreien Chinesischen Zwerghamster Ovarien (CHO)-System markiert. Zusätzlich konnte durch den Einsatz eines modifizierten tRNA/Aminoacyl-tRNA-Synthetase-Paares eine nicht-kanonische Aminosäure an Position eines integrierten Amber-Stopcodon in die Polypeptidkette eingebaut und die funktionelle Gruppe im Anschluss an einen Fluoreszenzfarbstoff gekoppelt werden. Aufgrund des offenen Charakters eignen sich zellfreie Proteinsynthesesysteme besonders für eine Integration von exogenen Komponenten in den Translationsprozess. Mit Hilfe der Fluoreszenzmarkierung wurde eine ligandvermittelte Konformationsänderung im Adora2a über einen Biolumineszenz-Resonanzenergietransfer detektiert. Durch die Etablierung der Amber-Suppression wurde darüber hinaus das Hormon Erythropoetin pegyliert, wodurch Eigenschaften wie Stabilität und Halbwertszeit des Proteins verändert wurden. Zu guter Letzt wurde ein neues tRNA/Aminoacyl-tRNA-Synthetase-Paar auf Basis der Methanosarcina mazei Pyrrolysin-Synthetase etabliert, um das Repertoire an nicht-kanonischen Aminosäuren und den damit verbundenen Kopplungsreaktionen zu erweitern. Zusammenfassend wurden die Potenziale zellfreier Systeme in Bezug auf der Herstellung von komplexen Membranproteinen und der Charakterisierung dieser durch die Einbringung einer positionsspezifischen Fluoreszenzmarkierung verdeutlicht, wodurch neue Möglichkeiten für die Analyse und Funktionalisierung von komplexen Proteinen geschaffen wurden. N2 - The functional characterization of therapeutically relevant proteins can be limited due to the provision of the target protein in adequate amounts. In particular membrane proteins belong to the so called “difficult-to-express” proteins because of possible cytotoxic side effects and a susceptibility to aggregation. The living organism can be circumvented by using cell lysates – the basic for cell-free protein synthesis. In the beginning of the thesis the ATP-dependent translation process in a cell lysate based on cultured insect (Sf21) cells was analyzed. For this purpose the translation of a nanoluciferase was regulated by the addition of an ATP-binding aptamer. The demonstrated application of aptamers in cell-free systems might enable a visualization of transcription and translation and following a potential validation process for high-throughput syntheses. In addition to the protein synthesis, factors such as posttranslational modifications and a correct integration into a lipid membrane are essential for the functionality of membrane proteins. Therefore, in the second part, integration of the G protein-coupled Endothelin receptor type B (ET-B) into the endogenous endoplasmic reticulum derived membranes and glycosylation were shown to be possible in a Sf21 cell-free system. Following to the successful synthesis of the ET-B receptor different fluorescent labeling strategies were applied to the adenosine receptor A2a (Adora2a). The first strategy applied precharged tRNAs, coupled to a fluorescently labeled amino acid, to the translation process in a Chinese Hamster Ovary cells (CHO) cell-free system. The second strategy utilized a modified tRNA/aminoacyl-tRNA-synthetase pair to incorporate a non-canonical amino acid at an integrated amber stop codon with a subsequently fluorescent labeling. The open character of cell-free systems enables a feasible integration of exogenous components into the translation process. The site-specific fluorescent labeling was the basis for the detection of a ligand-induced conformational change in the Adora2a by a bioluminescence resonance energy transfer. Additionally the amber suppression technique was transferred to the hormone Erythropoietin (EPO) to modify EPO´s stability and half-life period by coupling polyethylene glycol. Last but not least a novel tRNA/aminoacyl-tRNA-synthetase pair based on the Methanosarcina mazei pyrrolysine synthetase was developed to further increase the repertoire of non-canonical amino acids and copper-free click reactions. Summarizing in the present thesis the potentials of cell-free protein systems related to the synthesis of “difficult-to-express” proteins and the characterization of these proteins with site-specific fluorescence labeling are depicted, thereby establishing new methods for the analysis and functionalization of complex proteins. KW - Zellfreie Proteinsynthese KW - nicht-kanonische Aminosäuren KW - Klick-Chemie KW - Fluoreszenzmarkierung KW - GPCRs KW - Proteinmodifizierung KW - cell-free protein synthesis KW - non-canonical amino acids KW - click chemistry KW - fluorescent labeling KW - GPCRs KW - protein modification Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-442361 ER - TY - JOUR A1 - Wessig, Pablo A1 - Merkel, Roswitha A1 - Mueller, Peter T1 - Articulated rods - a novel class of molecular rods based on oligospiroketals (OSK) JF - Beilstein journal of organic chemistry N2 - We developed a new type of molecular rods consisting of two (or more) rigid units linked by a flexible joint. Consequently we called these constructs articulated rods (ARs). The syntheses of ARs were carried out by a flexible and modular approach providing access to a number of compounds with various functionalizations in terminal positions. First applications were presented with pyrene, cinnamoyl and anthracenyl labelled ARs. KW - articulated rods KW - click chemistry KW - molecular rods KW - oligospiroketals KW - pyrene excimer Y1 - 2015 U6 - https://doi.org/10.3762/bjoc.11.11 SN - 1860-5397 VL - 11 SP - 74 EP - 84 PB - Beilstein-Institut zur Förderung der Chemischen Wissenschaften CY - Frankfurt, Main ER - TY - JOUR A1 - Hüttl, Christine A1 - Hettrich, Cornelia A1 - Riedel, Melanie A1 - Henklein, Petra A1 - Rawel, Harshadrai Manilal A1 - Bier, Frank Fabian T1 - Development of Peptidyl Lysine Dendrons: 1,3-Dipolar Cycloaddition for Peptide Coupling and Antibody Recognition JF - Chemical biology & drug design N2 - A straightforward synthesis strategy to multimerize a peptide mimotopes for antibody B13-DE1 recognition is described based on lysine dendrons as multivalent scaffolds. Lysine dendrons that possess N-terminal alkyne residues at the periphery were quantitative functionalized with azido peptides using click chemistry. The solid-phase peptide synthesis (SPPS) allows preparing the peptide dendron in high purity and establishing the possibility of automation. The presented peptide dendron is a promising candidate as multivalent ligand and was used for antibody B13-DE1 recognition. The binding affinity increases with higher dendron generation without loss of specificity. The analysis of biospecific interaction between the synthesized peptide dendron and the antibody was done via surface plasmon resonance (SPR) technique. The presented results show a promising tool for investigations of antigen-antibody reactions. KW - click chemistry KW - lysine dendron KW - peptide mimotopes KW - solid-phase peptide synthesis KW - surface plasmon resonance Y1 - 2015 U6 - https://doi.org/10.1111/cbdd.12444 SN - 1747-0277 SN - 1747-0285 VL - 85 IS - 5 SP - 565 EP - 573 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Wessig, Pablo A1 - Budach, Dennis B. A1 - Thünemann, Andreas F. T1 - Dendrimers with Oligospiroketal (OSK) Building Blocks: Synthesis and Properties JF - Chemistry - a European journal N2 - The development of novel dendrimers containing oligospiroketal (OSK) rods as building blocks is described. The linkage between the core unit (CU), branching units (BU), and OSK rods relies on the CuAAC reaction between terminal alkynes and azides. Two different strategies of dendrimer synthesis were investigated and it was found that the convergent approach is clearly superior to the divergent one. SAXS measurements and MD simulations indicate that the obtained dendrimer features a globular structure with very low density. Obviously, the OSK rods stabilize a rather loose mass-fractal structure. KW - click chemistry KW - dendrimers KW - molecular rods KW - oxygen heterocycles KW - SAXS Y1 - 2015 U6 - https://doi.org/10.1002/chem.201501386 SN - 0947-6539 SN - 1521-3765 VL - 21 IS - 29 SP - 10466 EP - 10471 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Schwarze, Thomas A1 - Riemer, Janine A1 - Eidner, Sascha A1 - Holdt, Hans-Jürgen T1 - A Highly K+-Selective Two-Photon Fluorescent Probe JF - Chemistry - a European journal N2 - A highly K+-selective two-photon fluorescent probe for the in vitro monitoring of physiological K+ levels in the range of 1-100 mM is reported. The two-photon excited fluorescence (TPEF) probe shows a fluorescence enhancement (FE) by a factor of about three in the presence of 160 mM K+, independently of one-photon (OP, 430 nm) or two-photon (TP, 860 nm) excitation and comparable K+-induced FEs in the presence of competitive Na+ ions. The estimated dissociation constant (K-d) values in Na+-free solutions (K-d(OP)=(28 +/- 5) mM and K-d(TP)=(36 +/- 6) mM) and in combined K+/Na+ solutions (K-d(OP)=(38 +/- 8) mM and K-d(TP)=(46 +/- 25) mM) reflecting the high K+/Na+ selectivity of the fluorescent probe. The TP absorption cross-section (sigma(2PA)) of the TPEF probe+160 mMK(+) is 26 GM at 860 nm. Therefore, the TPEF probe is a suitable tool for the in vitro determination of K+. KW - click chemistry KW - fluorescence KW - fluorescent probes KW - potassium KW - two-photon Y1 - 2015 U6 - https://doi.org/10.1002/chem.201501473 SN - 0947-6539 SN - 1521-3765 VL - 21 IS - 32 SP - 11306 EP - 11310 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Schwarze, Thomas A1 - Garz, Andreas A1 - Teuchner, Klaus A1 - Menzel, Ralf A1 - Holdt, Hans-Jürgen T1 - Two-photon probes for metal ions based on phenylaza[18]crown-6 ethers and 1,2,3-triazoles as pi-linkers JF - ChemPhysChem : a European journal of chemical physics and physical chemistry KW - absorption KW - cations KW - click chemistry KW - dyes/pigments KW - fluorescence Y1 - 2014 U6 - https://doi.org/10.1002/cphc.201402232 SN - 1439-4235 SN - 1439-7641 VL - 15 IS - 12 SP - 2436 EP - 2439 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Ast, Sandra A1 - Fischer, Tobias A1 - Müller, Holger A1 - Mickler, Wulfhard A1 - Schwichtenberg, Mathias A1 - Rurack, Knut A1 - Holdt, Hans-Jürgen T1 - Integration of the 1,2,3-Triazole "Click" Motif as a potent signalling element in metal ion responsive fluorescent probes JF - Chemistry - a European journal N2 - In a systematic approach we synthesized a new series of fluorescent probes incorporating donoracceptor (D-A) substituted 1,2,3-triazoles as conjugative -linkers between the alkali metal ion receptor N-phenylaza-[18]crown-6 and different fluorophoric groups with different electron-acceptor properties (4-naphthalimide, meso-phenyl-BODIPY and 9-anthracene) and investigated their performance in organic and aqueous environments (physiological conditions). In the charge-transfer (CT) type probes 1, 2 and 7, the fluorescence is almost completely quenched by intramolecular CT (ICT) processes involving charge-separated states. In the presence of Na+ and K+ ICT is interrupted, which resulted in a lighting-up of the fluorescence in acetonitrile. Among the investigated fluoroionophores, compound 7, which contains a 9-anthracenyl moiety as the electron-accepting fluorophore, is the only probe which retains light-up features in water and works as a highly K+/Na+-selective probe under simulated physiological conditions. Virtually decoupled BODIPY-based 6 and photoinduced electron transfer (PET) type probes 35, where the 10-substituted anthracen-9-yl fluorophores are connected to the 1,2,3-triazole through a methylene spacer, show strong ion-induced fluorescence enhancement in acetonitrile, but not under physiological conditions. Electrochemical studies and theoretical calculations were used to assess and support the underlying mechanisms for the new ICT and PET 1,2,3-triazole fluoroionophores. KW - charge transfer KW - click chemistry KW - electron transfer KW - fluorescent probes KW - metal ions Y1 - 2013 U6 - https://doi.org/10.1002/chem.201201575 SN - 0947-6539 VL - 19 IS - 9 SP - 2990 EP - 3005 PB - Wiley-VCH CY - Weinheim ER - TY - THES A1 - Pfeifer, Sebastian T1 - Neue Ansätze zur Monomersequenzkontrolle in synthetischen Polymeren T1 - New approaches for monomer sequence control in synthetic polymers N2 - Von der Natur geschaffene Polymere faszinieren Polymerforscher durch ihre spezielle auf eine bestimmte Aufgabe ausgerichtete Funktionalität. Diese ergibt sich aus ihrer Bausteinabfolge uber die Ausbildung von Uberstrukturen. Dazu zählen zum Beispiel Proteine (Eiweiße), aus deren Gestalt sich wichtige Eigenschaften ergeben. Diese Struktureigenschaftsbeziehung gilt ebenso für funktionelle synthetische Makromoleküle. Demzufolge kann die Kontrolle der Monomersequenz in Polymeren bedeutend für die resultierende Form des Polymermoleküls sein. Obwohl die Synthese von synthetischen Polymeren mit der Komplexität und der Größe von Proteinen in absehbarer Zeit wahrscheinlich nicht gelingen wird, können wir von der Natur lernen, um neuartige Polymermaterialien mit definierten Strukturen (Sequenzen) zu synthetisieren. Deshalb ist die Entwicklung neuer und besserer Techniken zur Strukturkontrolle von großem Interesse für die Synthese von Makromolekülen, die perfekt auf ihre Funktion zugeschnitten sind. Im Gegensatz zu der Anzahl fortgeschrittener Synthesestrategien zum Design aus- gefallener Polymerarchitekturen – wie zum Beispiel Sterne oder baumartige Polymere (Dendrimere) – gibt es vergleichsweise wenig Ansätze zur echten Sequenzkontrolle in synthetischen Polymeren. Diese Arbeit stellt zwei unterschiedliche Techniken vor, mit denen die Monomersequenz innerhalb eines Polymers kontrolliert werden kann. Gerade bei den großtechnisch bedeutsamen radikalischen Polymerisationen ist die Sequenzkontrolle schwierig, weil die chemischen Bausteine (Monomere) sehr reaktiv sind. Im ersten Teil dieser Arbeit werden die Eigenschaften zweier Monomere (Styrol und N-substituiertes Maleinimid) geschickt ausgenutzt, um in eine Styrolkette definierte und lokal scharf abgegrenzte Funktionssequenzen einzubauen. Uber eine kontrollierte radikalische Polymerisationsmethode (ATRP) wurden in einer Ein-Topf-Synthese über das N-substituierte Maleinimid chemische Funktionen an einer beliebigen Stelle der Polystyrolkette eingebaut. Es gelang ebenfalls, vier unterschiedliche Funktionen in einer vorgegebenen Sequenz in die Polymerkette einzubauen. Diese Technik wurde an zwanzig verschiedenen N-substituierten Maleinimiden getestet, die meisten konnten erfolgreich in die Polymerkette integriert werden. In dem zweiten in dieser Arbeit vorgestellten Ansatz zur Sequenzkontrolle, wurde der schrittweise Aufbau eines Oligomers aus hydrophoben und hydrophilen Segmenten (ω-Alkin-Carbonsäure bzw. α-Amin-ω-Azid-Oligoethylenglycol) an einem löslichen Polymerträger durchgeführt. Das Oligomer konnte durch die geschickte Auswahl der Verknüpfungsreaktionen ohne Schutzgruppenstrategie synthetisiert werden. Der lösliche Polymerträger aus Polystyrol wurde mittels ATRP selbst synthetisiert. Dazu wurde ein Startreagenz (Initiator) entwickelt, das in der Mitte einen säurelabilen Linker, auf der einen Seite die initiierende Einheit und auf der anderen die Ankergruppe für die Anbindung des ersten Segments trägt. Der lösliche Polymerträger ermöglichte einerseits die schrittweise Synthese in Lösung. Andererseits konnten überschüssige Reagenzien und Nebenprodukte zwischen den Reaktionsschritten durch Fällung in einem Nicht-Lösungsmittel einfach abgetrennt werden. Der Linker ermöglichte die Abtrennung des Oligomers aus jeweils drei hydrophoben und hydrophilen Einheiten nach der Synthese. N2 - Polymer scientists are impressed by polymers created by nature. This is caused by their structure which is aimed to fulfill very special functions. The structure is primary built by sequential covalent linking of building units. Secondly, supramolecular aggregation leads to three-dimensional alignment. The sequence of the building blocks has a high influence on the higher molecular arrangement. Proteins are only one example for supramolecular structures which have special functions because of their supramolecular arrangement. This structure-property relationship is also possible for synthetic polymers. For this reason the control of monomer sequences in synthtic polymers is just as important for the resulting structure of a synthetic polymer molecule. Even though the synthesis of polymers with complex strucures and sizes as in nature is impossible in near future. But the development of new and better techniques for sequence control in synthetic polymers is of high importance to create well defined macromolecular structures which are tailor-made for their function. In contrast to a lot of advanced synthethis strategies for the design of complex polymer architechtures (e.g. brushes, stars, or dendrimers) their are less approaches for a monomer sequence control in synthetic polymers. This work presents two different techniques for controlling the monomer sequence inside a polymer. Especially in technologically significant radical polymerization it is difficult to control the monomer sequence because radical species are very reactive and the addition of a monomer to the radical function is not selective. The first approach makes use of the properties of two monomers (styrene and N-substituted maleimides) to add chemical funtions locally inside a polystyrene chain. By addition of N-functionalized maleimides during the polymerization of styrene chemical functions could be added at any desired position inside the polystyrene chain. This technique was tested on 20 different N-substituted maleimides. Most of them were incorporated successfully into the polymer chain. The second monomer sequence control approach is a stepwise synthesis of an oligomer made of short alternating hydrophobic and hydrophilic segments on a soluble polymer support. Two building blocks were used: ω-alkyne carboxylic acid (A-B) and α-amine-ω-azide oligoethylene glycol (C-D). The linking of the segments was done by applying two very efficient chemical reactions, namely 1,3-dipolar cycloaddition of terminal alkynes (A) and azides (D) and amidification of carboxylic acids (B) with primary amines (C). These two reactions proceed chemoselectively in an ABCD multifunctional mixture without a protection chemistry strategy. The polystyrene support was synthesized by atom transfer radical polymerization (ATRP) in the presence of an azido-functionalized ATRP initiator containing a labile p-alkoxybenzyl ester linker. Depending on the choise of solvent, the soluble polymer support was used in solution during the coupling reactions or was precipitated for an easy removal of excessive reagents and by-products. The acid-labile linker could be cleaved by trifluoroacetic acid treatment to obtain a hydrophilic/hydrophobic block copolymer. KW - ATRP KW - Copolymerisation KW - Flüssigphasensynthese KW - WANG-Linker KW - Klick-Chemie KW - ATRP KW - copolymerization KW - liquid phase synthesis KW - WANG-linker KW - click chemistry Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-51385 ER - TY - THES A1 - Hahn, Harald T1 - Modularer Ansatz zu multifunktionellen Polymer-Peptid-Fasern T1 - Modular strategy to multifunctional polymer-peptide-fibers N2 - Die Kombination von Polymeren mit Peptiden vereint die Eigenschaften beider Stoffklassen miteinander. Dabei können die strukturbildenden Eigenschaften der Peptide genutzt werden, um Polymere zu organisieren. In der vorliegenden Arbeit wurde ein Polymer-Peptid-Konjugat verwendet, das sich in Wasser zu Bändern anordnet. Die treibende Kraft für diesen Prozess ist die Anordnung des Peptidteils zu β-Faltblattstrukturen. Das Polymer-Peptid-Aggregat besitzt einen Peptidkern mit funktionalen Oberflächen, der lateral von einer Polyethylenoxidschale umgeben ist. Durch Änderung der Peptidsequenz war es bisher möglich, die Eigenschaften dieser Fasern zu variieren. In der Arbeit wird ein modularer Ansatz zur vielfältigen Modifizierung einer Polymer-Peptid-Faser entwickelt. So ist es möglich, die Eigenschaften der Fasern einzustellen, ohne die strukturbildende β-Faltblattsequenz verändern zu müssen. Um weitere Funktionen an den Fasern anzubringen, wurde die 1,3-dipolaren Addition verwendet. Diese Reaktion beschreibt die konzertierte Umlagerung eines Azides mit einem Alkin. Sie ist in den meisten Lösungsmitteln unter hohen Ausbeuten durchführbar. Im Rahmen der Arbeit wird die Erzeugung von Aziden untersucht und auf die Polymer-Peptid-Fasern übertragen. Der Diazotransfer stellte dabei die Methode der Wahl dar, so können Azidgruppen aus Aminen gewonnen werden. Unter Verwendung der 1,3-dipolaren Addition konnten verschiedene alkinfunktionale Moleküle kovalent an die azidfunktionalisierten Polymer-Peptid-Fasern gebunden werden. So wurde ein Fluoreszenzfarbstoff an die Fasern gebunden, der eine Abbildung der Fasern mittels konfokaler Mikroskopie erlaubte. Weiterhin wurden die Eigenschaften der Fasern durch Addition dreier carboxylfunktionaler Moleküle modifiziert. Diese Fasern konnten weiter genutzt werden, um Kalzium zu binden. Dabei variierte die Anzahl der gebundenen Kalziumionen in Abhängigkeit der jeweiligen Fasermodifikation erheblich. Weitere Untersuchungen, die Morphologie von Kalziumcarbonatkristallen betreffend, werden aktuell durchgeführt. Die kovalente Anbringung eines reduzierenden Zuckers an die Polymer-Peptid-Fasern erlaubt die Abscheidung von Silber aus Tollens Reagenz. Durch eine Entwicklung analog zur Schwarz-Weiss-Photographie können in nachfolgenden Arbeiten so Silberdrähte in Nanogröße erzeugt werden. An die azidfunktionalen Fasern können weitere funktionale Moleküle angebracht werden, um die Eigenschaften und das Anwendungsspektrum der Polymer-Peptid-Fasern zu erweitern. N2 - The combination of polymer with peptides combines the advantages of both substance classes. It is possible to use peptide structure-forming properties to assemble polymers. In my current research, a self assembling Polymer-Peptide-Conjugate was used, which forms ribbon-like structures in water. The peptide tendency to form β-sheets is the driving force for this process. The resulting Polymer-Peptide-Aggregate is build up of a core shell model, where the peptides are the core and the polymer (polyethylene oxide) is the lateral suited shell. A new peptide synthesis was necessary in order to change the functional groups in the peptide core. In my present work a modular strategy was developed to get access to various types of modified Polymer-Peptide-Fiber. This allows adjustiment to the fiber properties without changing the structure forming b‑sheet sequence. To apply these functions, 1,3‑dipolar addition was used. This reaction described the simultaneous reactions of alkynes and azides. The reaction occurs in most solvents under high yields. In the context of this work, the generation of azides was investigated and transferred to the Polymer-Peptide-Fibers. Diazotransfer was the chosen method to transfer primary amines into azidefunctions at the fiber surface. With the use of 1,3‑dipolar addition it was possible to bind alkyne functionalized molecules covalent to the azide functionalized fibers. A fluorescent dye was bound to the fibers to image these fibers with confocal microscopy. The properties of the azide fibers were further modified to incorporation three different carboxylic molecules. These fibers were used to estimate the calcium binding affinity. Thus, differing the number of bonded calcium is a function of the used fiber attachment. Investigations concerning the morphology of Calcium carbonate crystals can be done. The covalent attachment of reducing sugar to the Polymer-Peptide-Fibers should will allow the production of silver(0)clusters along the fibers with the use of Tollens´ reagent. With the help of a developer solution, similar to black and white photography, the possibility to archive silverrods in nanometer size can be obtained. The applied modifications on fibers is hence a promising first step in altering fibers in which by adjusting its properties, we broaden the applications of these Polymer-Peptide-Fibers. KW - Polymer KW - Peptide KW - selbstanordnend KW - Klick Chemie KW - Dizotransfer KW - polymer KW - peptide KW - selfassembling KW - click chemistry KW - diazotransfer Y1 - 2009 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-33016 ER -