@phdthesis{Ketzer2024,
  author    = {Ketzer, Laura},
  title     = {The impact of stellar activity evolution on atmospheric mass loss of young exoplanets},
  doi       = {10.25932/publishup-62681},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-626819},
  school      = {Universit{\"a}t Potsdam},
  pages     = {x, 208},
  year      = {2024},
  abstract  = {The increasing number of known exoplanets raises questions about their demographics and the mechanisms that shape planets into how we observe them today. Young planets in close-in orbits are exposed to harsh environments due to the host star being magnetically highly active, which results in high X-ray and extreme UV fluxes impinging on the planet. Prolonged exposure to this intense photoionizing radiation can cause planetary atmospheres to heat up, expand and escape into space via a hydrodynamic escape process known as photoevaporation. For super-Earth and sub-Neptune-type planets, this can even lead to the complete erosion of their primordial gaseous atmospheres. A factor of interest for this particular mass-loss process is the activity evolution of the host star. Stellar rotation, which drives the dynamo and with it the magnetic activity of a star, changes significantly over the stellar lifetime. This strongly affects the amount of high-energy radiation received by a planet as stars age. At a young age, planets still host warm and extended envelopes, making them particularly susceptible to atmospheric evaporation. Especially in the first gigayear, when X-ray and UV levels can be 100 - 10,000 times higher than for the present-day sun, the characteristics of the host star and the detailed evolution of its high-energy emission are of importance. In this thesis, I study the impact of stellar activity evolution on the high-energy-induced atmospheric mass loss of young exoplanets. The PLATYPOS code was developed as part of this thesis to calculate photoevaporative mass-loss rates over time. The code, which couples parameterized planetary mass-radius relations with an analytical hydrodynamic escape model, was used, together with Chandra and eROSITA X-ray observations, to investigate the future mass loss of the two young multiplanet systems V1298 Tau and K2-198. Further, in a numerical ensemble study, the effect of a realistic spread of activity tracks on the small-planet radius gap was investigated for the first time. The works in this thesis show that for individual systems, in particular if planetary masses are unconstrained, the difference between a young host star following a low-activity track vs. a high-activity one can have major implications: the exact shape of the activity evolution can determine whether a planet can hold on to some of its atmosphere, or completely loses its envelope, leaving only the bare rocky core behind. For an ensemble of simulated planets, an observationally-motivated distribution of activity tracks does not substantially change the final radius distribution at ages of several gigayears. My simulations indicate that the overall shape and slope of the resulting small-planet radius gap is not significantly affected by the spread in stellar activity tracks. However, it can account for a certain scattering or fuzziness observed in and around the radius gap of the observed exoplanet population.},
  language  = {en}
}
@phdthesis{Arend2024,
  author    = {Arend, Marius},
  title     = {Comparing genome-scale models of protein-constrained metabolism in heterotrophic and photosynthetic microorganisms},
  doi       = {10.25932/publishup-65147},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-651470},
  school      = {Universit{\"a}t Potsdam},
  pages     = {150},
  year      = {2024},
  abstract  = {Genome-scale metabolic models are mathematical representations of all known reactions occurring in a cell. Combined with constraints based on physiological measurements, these models have been used to accurately predict metabolic fluxes and effects of perturbations (e.g. knock-outs) and to inform metabolic engineering strategies. Recently, protein-constrained models have been shown to increase predictive potential (especially in overflow metabolism), while alleviating the need for measurement of nutrient uptake rates. The resulting modelling frameworks quantify the upkeep cost of a certain metabolic flux as the minimum amount of enzyme required for catalysis. These improvements are based on the use of in vitro turnover numbers or in vivo apparent catalytic rates of enzymes for model parameterization. In this thesis several tools for the estimation and refinement of these parameters based on in vivo proteomics data of Escherichia coli, Saccharomyces cerevisiae, and Chlamydomonas reinhardtii have been developed and applied. The difference between in vitro and in vivo catalytic rate measures for the three microorganisms was systematically analyzed. The results for the facultatively heterotrophic microalga C. reinhardtii considerably expanded the apparent catalytic rate estimates for photosynthetic organisms. Our general finding pointed at a global reduction of enzyme efficiency in heterotrophy compared to other growth scenarios. Independent of the modelled organism, in vivo estimates were shown to improve accuracy of predictions of protein abundances compared to in vitro values for turnover numbers. To further improve the protein abundance predictions, machine learning models were trained that integrate features derived from protein-constrained modelling and codon usage. Combining the two types of features outperformed single feature models and yielded good prediction results without relying on experimental transcriptomic data. The presented work reports valuable advances in the prediction of enzyme allocation in unseen scenarios using protein constrained metabolic models. It marks the first successful application of this modelling framework in the biotechnological important taxon of green microalgae, substantially increasing our knowledge of the enzyme catalytic landscape of phototrophic microorganisms.},
  language  = {en}
}
@phdthesis{Wischnewski2011,
  author    = {Wischnewski, Juliane},
  title     = {Reconstructing climate variability on the Tibetan Plateau : comparing aquatic and terrestrial signals},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-52453},
  school      = {Universit{\"a}t Potsdam},
  year      = {2011},
  abstract  = {Spatial and temporal temperature and moisture patterns across the Tibetan Plateau are very complex. The onset and magnitude of the Holocene climate optimum in the Asian monsoon realm, in particular, is a subject of considerable debate as this time period is often used as an analogue for recent global warming. In the light of contradictory inferences regarding past climate and environmental change on the Tibetan Plateau, I have attempted to explain mismatches in the timing and magnitude of change. Therefore, I analysed the temporal variation of fossil pollen and diatom spectra and the geochemical record from palaeo-ecological records covering different time scales (late Quaternary and the last 200 years) from two core regions in the NE and SE Tibetan Plateau. For interpretation purposes I combined my data with other available palaeo-ecological data to set up corresponding aquatic and terrestrial proxy data sets of two lake pairs and two sets of sites. I focused on the direct comparison of proxies representing lacustrine response to climate signals (e.g., diatoms, ostracods, geochemical record) and proxies representing changes in the terrestrial environment (i.e., terrestrial pollen), in order to asses whether the lake and its catchments respond at similar times and magnitudes to environmental changes. Therefore, I introduced the established numerical technique procrustes rotation as a new approach in palaeoecology to quantitatively compare raw data of any two sedimentary records of interest in order to assess their degree of concordance. Focusing on the late Quaternary, sediment cores from two lakes (Kuhai Lake 35.3°N; 99.2°E; 4150 m asl; and Koucha Lake 34.0°N; 97.2°E; 4540 m asl) on the semi-arid northeastern Tibetan Plateau were analysed to identify post-glacial vegetation and environmental changes, and to investigate the responses of lake ecosystems to such changes. Based on the pollen record, five major vegetation and climate changes could be identified: (1) A shift from alpine desert to alpine steppe indicates a change from cold, dry conditions to warmer and more moist conditions at 14.8 cal. ka BP, (2) alpine steppe with tundra elements points to conditions of higher effective moisture and a stepwise warming climate at 13.6 cal. ka BP, (3) the appearance of high-alpine meadow vegetation indicates a further change towards increased moisture, but with colder temperatures, at 7.0 cal. ka BP, (4) the reoccurrence of alpine steppe with desert elements suggests a return to a significantly colder and drier phase at 6.3 cal. ka BP, and (5) the establishment of alpine steppe-meadow vegetation indicates a change back to relatively moist conditions at 2.2 cal. ka BP. To place the reconstructed climate inferences from the NE Tibetan Plateau into the context of Holocene moisture evolution across the Tibetan Plateau, I applied a five-scale moisture index and average link clustering to all available continuous pollen and non-pollen palaeoclimate records from the Tibetan Plateau, in an attempt to detect coherent regional and temporal patterns of moisture evolution on the Plateau. However, no common temporal or spatial pattern of moisture evolution during the Holocene could be detected, which can be assigned to the complex responses of different proxies to environmental changes in an already very heterogeneous mountain landscape, where minor differences in elevation can result in marked variations in microenvironments. Focusing on the past 200 years, I analysed the sedimentary records (LC6 Lake 29.5°N, 94.3°E, 4132 m asl; and Wuxu Lake 29.9°N, 101.1°E, 3705 m asl) from the southeastern Tibetan Plateau. I found that despite presumed significant temperature increases over that period, pollen and diatom records from the SE Tibetan Plateau reveal only very subtle changes throughout their profiles. The compositional species turnover investigated over the last 200 years appears relatively low in comparison to the species reorganisations during the Holocene. The results indicate that climatically induced ecological thresholds are not yet crossed, but that human activity has an increasing influence, particularly on the terrestrial ecosystem. Forest clearances and reforestation have not caused forest decline in our study area, but a conversion of natural forests to semi-natural secondary forests. The results from the numerical proxy comparison of the two sets of two pairs of Tibetan lakes indicate that the use of different proxies and the work with palaeo-ecological records from different lake types can cause deviant stories of inferred change. Irrespective of the timescale (Holocene or last 200 years) or region (SE or NE Tibetan Plateau) analysed, the agreement in terms of the direction, timing, and magnitude of change between the corresponding terrestrial data sets is generally better than the match between the corresponding lacustrine data sets, suggesting that lacustrine proxies may partly be influenced by in-lake or local catchment processes whereas the terrestrial proxy reflects a more regional climatic signal. The current disaccord on coherent temporal and spatial climate patterns on the Tibetan Plateau can partly be ascribed to the complexity of proxy response and lake systems on the Tibetan Plateau. Therefore, a multi-proxy, multi-site approach is important in order to gain a reliable climate interpretation for the complex mountain landscape of the Tibetan Plateau.},
  language  = {en}
}
@phdthesis{Zeuschner2022,
  author    = {Zeuschner, Steffen Peer},
  title     = {Magnetoacoustics observed with ultrafast x-ray diffraction},
  doi       = {10.25932/publishup-56109},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-561098},
  school      = {Universit{\"a}t Potsdam},
  pages     = {V, 128, IX},
  year      = {2022},
  abstract  = {In the present thesis I investigate the lattice dynamics of thin film hetero structures of magnetically ordered materials upon femtosecond laser excitation as a probing and manipulation scheme for the spin system. The quantitative assessment of laser induced thermal dynamics as well as generated picosecond acoustic pulses and their respective impact on the magnetization dynamics of thin films is a challenging endeavor. All the more, the development and implementation of effective experimental tools and comprehensive models are paramount to propel future academic and technological progress. In all experiments in the scope of this cumulative dissertation, I examine the crystal lattice of nanoscale thin films upon the excitation with femtosecond laser pulses. The relative change of the lattice constant due to thermal expansion or picosecond strain pulses is directly monitored by an ultrafast X-ray diffraction (UXRD) setup with a femtosecond laser-driven plasma X-ray source (PXS). Phonons and spins alike exert stress on the lattice, which responds according to the elastic properties of the material, rendering the lattice a versatile sensor for all sorts of ultrafast interactions. On the one hand, I investigate materials with strong magneto-elastic properties; The highly magnetostrictive rare-earth compound TbFe2, elemental Dysprosium or the technological relevant Invar material FePt. On the other hand I conduct a comprehensive study on the lattice dynamics of Bi1Y2Fe5O12 (Bi:YIG), which exhibits high-frequency coherent spin dynamics upon femtosecond laser excitation according to the literature. Higher order standing spinwaves (SSWs) are triggered by coherent and incoherent motion of atoms, in other words phonons, which I quantified with UXRD. We are able to unite the experimental observations of the lattice and magnetization dynamics qualitatively and quantitatively. This is done with a combination of multi-temperature, elastic, magneto-elastic, anisotropy and micro-magnetic modeling. The collective data from UXRD, to probe the lattice, and time-resolved magneto-optical Kerr effect (tr-MOKE) measurements, to monitor the magnetization, were previously collected at different experimental setups. To improve the precision of the quantitative assessment of lattice and magnetization dynamics alike, our group implemented a combination of UXRD and tr-MOKE in a singular experimental setup, which is to my knowledge, the first of its kind. I helped with the conception and commissioning of this novel experimental station, which allows the simultaneous observation of lattice and magnetization dynamics on an ultrafast timescale under identical excitation conditions. Furthermore, I developed a new X-ray diffraction measurement routine which significantly reduces the measurement time of UXRD experiments by up to an order of magnitude. It is called reciprocal space slicing (RSS) and utilizes an area detector to monitor the angular motion of X-ray diffraction peaks, which is associated with lattice constant changes, without a time-consuming scan of the diffraction angles with the goniometer. RSS is particularly useful for ultrafast diffraction experiments, since measurement time at large scale facilities like synchrotrons and free electron lasers is a scarce and expensive resource. However, RSS is not limited to ultrafast experiments and can even be extended to other diffraction techniques with neutrons or electrons.},
  language  = {en}
}
@phdthesis{Videla2014,
  author    = {Videla, Santiago},
  title     = {Reasoning on the response of logical signaling networks with answer set programming},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-71890},
  school      = {Universit{\"a}t Potsdam},
  year      = {2014},
  abstract  = {Deciphering the functioning of biological networks is one of the central tasks in systems biology. In particular, signal transduction networks are crucial for the understanding of the cellular response to external and internal perturbations. Importantly, in order to cope with the complexity of these networks, mathematical and computational modeling is required. We propose a computational modeling framework in order to achieve more robust discoveries in the context of logical signaling networks. More precisely, we focus on modeling the response of logical signaling networks by means of automated reasoning using Answer Set Programming (ASP). ASP provides a declarative language for modeling various knowledge representation and reasoning problems. Moreover, available ASP solvers provide several reasoning modes for assessing the multitude of answer sets. Therefore, leveraging its rich modeling language and its highly efficient solving capacities, we use ASP to address three challenging problems in the context of logical signaling networks: learning of (Boolean) logical networks, experimental design, and identification of intervention strategies. Overall, the contribution of this thesis is three-fold. Firstly, we introduce a mathematical framework for characterizing and reasoning on the response of logical signaling networks. Secondly, we contribute to a growing list of successful applications of ASP in systems biology. Thirdly, we present a software providing a complete pipeline for automated reasoning on the response of logical signaling networks.},
  language  = {en}
}
@phdthesis{Brill2022,
  author    = {Brill, Fabio Alexander},
  title     = {Applications of machine learning and open geospatial data in flood risk modelling},
  doi       = {10.25932/publishup-55594},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-555943},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xix, 124},
  year      = {2022},
  abstract  = {Der technologische Fortschritt erlaubt es, zunehmend komplexe Vorhersagemodelle auf Basis immer gr{\"o}ßerer Datens{\"a}tze zu produzieren. F{\"u}r das Risikomanagement von Naturgefahren sind eine Vielzahl von Modellen als Entscheidungsgrundlage notwendig, z.B. in der Auswertung von Beobachtungsdaten, f{\"u}r die Vorhersage von Gefahrenszenarien, oder zur statistischen Absch{\"a}tzung der zu erwartenden Sch{\"a}den. Es stellt sich also die Frage, inwiefern moderne Modellierungsans{\"a}tze wie das maschinelle Lernen oder Data-Mining in diesem Themenbereich sinnvoll eingesetzt werden k{\"o}nnen. Zus{\"a}tzlich ist im Hinblick auf die Datenverf{\"u}gbarkeit und -zug{\"a}nglichkeit ein Trend zur {\"O}ffnung (open data) zu beobachten. Thema dieser Arbeit ist daher, die M{\"o}glichkeiten und Grenzen des maschinellen Lernens und frei verf{\"u}gbarer Geodaten auf dem Gebiet der Hochwasserrisikomodellierung im weiteren Sinne zu untersuchen. Da dieses {\"u}bergeordnete Thema sehr breit ist, werden einzelne relevante Aspekte herausgearbeitet und detailliert betrachtet. Eine prominente Datenquelle im Bereich Hochwasser ist die satellitenbasierte Kartierung von {\"U}berflutungsfl{\"a}chen, die z.B. {\"u}ber den Copernicus Service der Europ{\"a}ischen Union frei zur Verf{\"u}gung gestellt werden. Große Hoffnungen werden in der wissenschaftlichen Literatur in diese Produkte gesetzt, sowohl f{\"u}r die akute Unterst{\"u}tzung der Einsatzkr{\"a}fte im Katastrophenfall, als auch in der Modellierung mittels hydrodynamischer Modelle oder zur Schadensabsch{\"a}tzung. Daher wurde ein Fokus in dieser Arbeit auf die Untersuchung dieser Flutmasken gelegt. Aus der Beobachtung, dass die Qualit{\"a}t dieser Produkte in bewaldeten und urbanen Gebieten unzureichend ist, wurde ein Verfahren zur nachtr{\"a}glichenVerbesserung mittels maschinellem Lernen entwickelt. Das Verfahren basiert auf einem Klassifikationsalgorithmus der nur Trainingsdaten von einer vorherzusagenden Klasse ben{\"o}tigt, im konkreten Fall also Daten von {\"U}berflutungsfl{\"a}chen, nicht jedoch von der negativen Klasse (trockene Gebiete). Die Anwendung f{\"u}r Hurricane Harvey in Houston zeigt großes Potenzial der Methode, abh{\"a}ngig von der Qualit{\"a}t der urspr{\"u}nglichen Flutmaske. Anschließend wird anhand einer prozessbasierten Modellkette untersucht, welchen Einfluss implementierte physikalische Prozessdetails auf das vorhergesagte statistische Risiko haben. Es wird anschaulich gezeigt, was eine Risikostudie basierend auf etablierten Modellen leisten kann. Solche Modellketten sind allerdings bereits f{\"u}r Flusshochwasser sehr komplex, und f{\"u}r zusammengesetzte oder kaskadierende Ereignisse mit Starkregen, Sturzfluten, und weiteren Prozessen, kaum vorhanden. Im vierten Kapitel dieser Arbeit wird daher getestet, ob maschinelles Lernen auf Basis von vollst{\"a}ndigen Schadensdaten einen direkteren Weg zur Schadensmodellierung erm{\"o}glicht, der die explizite Konzeption einer solchen Modellkette umgeht. Dazu wird ein staatlich erhobener Datensatz der gesch{\"a}digten Geb{\"a}ude w{\"a}hrend des schweren El Ni{\~n}o Ereignisses 2017 in Peru verwendet. In diesem Kontext werden auch die M{\"o}glichkeiten des Data-Mining zur Extraktion von Prozessverst{\"a}ndnis ausgelotet. Es kann gezeigt werden, dass diverse frei verf{\"u}gbare Geodaten n{\"u}tzliche Informationen f{\"u}r die Gefahren- und Schadensmodellierung von komplexen Flutereignissen liefern, z.B. satellitenbasierte Regenmessungen, topographische und hydrographische Information, kartierte Siedlungsfl{\"a}chen, sowie Indikatoren aus Spektraldaten. Zudem zeigen sich Erkenntnisse zu den Sch{\"a}digungsprozessen, die im Wesentlichen mit den vorherigen Erwartungen in Einklang stehen. Die maximale Regenintensit{\"a}t wirkt beispielsweise in St{\"a}dten und steilen Schluchten st{\"a}rker sch{\"a}digend, w{\"a}hrend die Niederschlagssumme in tiefliegenden Flussgebieten und bewaldeten Regionen als aussagekr{\"a}ftiger befunden wurde. L{\"a}ndliche Gebiete in Peru weisen in der pr{\"a}sentierten Studie eine h{\"o}here Vulnerabilit{\"a}t als die Stadtgebiete auf. Jedoch werden auch die grunds{\"a}tzlichen Grenzen der Methodik und die Abh{\"a}ngigkeit von spezifischen Datens{\"a}tzen and Algorithmen offenkundig. In der {\"u}bergreifenden Diskussion werden schließlich die verschiedenen Methoden - prozessbasierte Modellierung, pr{\"a}diktives maschinelles Lernen, und Data-Mining - mit Blick auf die Gesamtfragestellungen evaluiert. Im Bereich der Gefahrenbeobachtung scheint eine Fokussierung auf neue Algorithmen sinnvoll. Im Bereich der Gefahrenmodellierung, insbesondere f{\"u}r Flusshochwasser, wird eher die Verbesserung von physikalischen Modellen, oder die Integration von prozessbasierten und statistischen Verfahren angeraten. In der Schadensmodellierung fehlen nach wie vor die großen repr{\"a}sentativen Datens{\"a}tze, die f{\"u}r eine breite Anwendung von maschinellem Lernen Voraussetzung ist. Daher ist die Verbesserung der Datengrundlage im Bereich der Sch{\"a}den derzeit als wichtiger einzustufen als die Auswahl der Algorithmen.},
  language  = {en}
}
@phdthesis{Schifferle2024,
  author    = {Schifferle, Lukas},
  title     = {Optical properties of (Mg,Fe)O at high pressure},
  doi       = {10.25932/publishup-62216},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-622166},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XIV, 90},
  year      = {2024},
  abstract  = {Large parts of the Earth's interior are inaccessible to direct observation, yet global geodynamic processes are governed by the physical material properties under extreme pressure and temperature conditions. It is therefore essential to investigate the deep Earth's physical properties through in-situ laboratory experiments. With this goal in mind, the optical properties of mantle minerals at high pressure offer a unique way to determine a variety of physical properties, in a straight-forward, reproducible, and time-effective manner, thus providing valuable insights into the physical processes of the deep Earth. This thesis focusses on the system Mg-Fe-O, specifically on the optical properties of periclase (MgO) and its iron-bearing variant ferropericlase ((Mg,Fe)O), forming a major planetary building block. The primary objective is to establish links between physical material properties and optical properties. In particular the spin transition in ferropericlase, the second-most abundant phase of the lower mantle, is known to change the physical material properties. Although the spin transition region likely extends down to the core-mantle boundary, the ef-fects of the mixed-spin state, where both high- and low-spin state are present, remains poorly constrained. In the studies presented herein, we show how optical properties are linked to physical properties such as electrical conductivity, radiative thermal conductivity and viscosity. We also show how the optical properties reveal changes in the chemical bonding. Furthermore, we unveil how the chemical bonding, the optical and other physical properties are affected by the iron spin transition. We find opposing trends in the pres-sure dependence of the refractive index of MgO and (Mg,Fe)O. From 1 atm to ~140 GPa, the refractive index of MgO decreases by ~2.4\% from 1.737 to 1.696 (±0.017). In contrast, the refractive index of (Mg0.87Fe0.13)O (Fp13) and (Mg0.76Fe0.24)O (Fp24) ferropericlase increases with pressure, likely because Fe Fe interactions between adjacent iron sites hinder a strong decrease of polarizability, as it is observed with increasing density in the case of pure MgO. An analysis of the index dispersion in MgO (decreasing by ~23\% from 1 atm to ~103 GPa) reflects a widening of the band gap from ~7.4 eV at 1 atm to ~8.5 (±0.6) eV at ~103 GPa. The index dispersion (between 550 and 870 nm) of Fp13 reveals a decrease by a factor of ~3 over the spin transition range (~44-100 GPa). We show that the electrical band gap of ferropericlase significantly widens up to ~4.7 eV in the mixed spin region, equivalent to an increase by a factor of ~1.7. We propose that this is due to a lower electron mobility between adjacent Fe2+ sites of opposite spin, explaining the previously observed low electrical conductivity in the mixed spin region. From the study of absorbance spectra in Fp13, we show an increasing covalency of the Fe-O bond with pressure for high-spin ferropericlase, whereas in the low-spin state a trend to a more ionic nature of the Fe-O bond is observed, indicating a bond weakening effect of the spin transition. We found that the spin transition is ultimately caused by both an increase of the ligand field-splitting energy and a decreasing spin-pairing energy of high-spin Fe2+.},
  language  = {en}
}
@phdthesis{Martin2024,
  author    = {Martin, Johannes},
  title     = {Synthesis of protein-polymer conjugates and block copolymers via sortase-mediated ligation},
  doi       = {10.25932/publishup-64566},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-645669},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XVII, 150},
  year      = {2024},
  abstract  = {In den vergangenen Jahrzehnten haben therapeutische Proteine in der pharmazeutischen Industrie mehr und mehr an Bedeutung gewonnen. Werden Proteine nichtmenschlichen Ursprungs verwendet, kann es jedoch zu einer Immunreaktion kommen, sodass das Protein sehr schnell aus dem K{\"o}rper ausgeschieden oder abgebaut wird. Um die Zirkulationszeit im Blut signifikant zu verl{\"a}ngern, werden die Proteine mit synthetischen Polymeren modifiziert (Protein-Polymer-Konjugate). Die Proteine aller heute auf dem Markt erh{\"a}ltlichen Medikamente dieser Art tragen eine oder mehrere Polymerketten aus Poly(ethylenglycol) (PEG). Ein Nachteil der PEGylierung ist, dass viele Patienten bei regelm{\"a}ßiger Einnahme dieser Medikamente Antik{\"o}rper gegen PEG entwickeln, die den effizienzsteigernden Effekt der PEGylierung wieder aufheben. Ein weiterer Nachteil der PEGylierung ist die oftmals deutlich verringerte Aktivit{\"a}t der Konjugate im Vergleich zum nativen Protein. Der Grund daf{\"u}r ist die Herstellungsmethode der Konjugate, bei der meist die prim{\"a}ren Amine der Lysin-Seitenketten und der N-Terminus des Proteins genutzt werden. Da die meisten Proteine mehrere gut zug{\"a}ngliche Lysine aufweisen, werden oft unterschiedliche und teilweise mehrere Lysine mit PEG funktionalisiert, was zu einer Mischung an Regioisomeren f{\"u}hrt. Je nach Position der PEG-Kette kann das aktive Zentrum abgeschirmt oder die 3D-Struktur des Proteins ver{\"a}ndert werden, was zu einem teilweise drastischen Aktivit{\"a}tsabfall f{\"u}hrt. In dieser Arbeit wurde eine neuartige Methode zur Ligation von Makromolek{\"u}len untersucht. Die Verwendung eines Enzyms als Katalysator zur Verbindung zweier Makromolek{\"u}le ist bisher wenig untersucht und ineffizient. Als Enzym wurde Sortase A ausgew{\"a}hlt, eine gut untersuchte Ligase aus der Familie der Transpeptidasen, welche die Ligation zweier Peptide katalysieren kann. Ein Nachteil dieser Sortase-vermittelten Ligation ist, dass es sich um eine Gleichgewichtsreaktion handelt, wodurch hohe Ausbeuten schwierig zu erreichen sind. Im Rahmen dieser Dissertation wurden zwei zuvor entwickelte Methoden zur Verschiebung des Gleichgewichts ohne Einsatz eines großen {\"U}berschusses von einem Edukt f{\"u}r Makromolek{\"u}le {\"u}berpr{\"u}ft. Zur Durchf{\"u}hrung der Sortase-vermittelten Ligation werden zwei komplement{\"a}re Peptidsequenzen verwendet, die Erkennungssequenz und das Nukleophil. Um eine systematische Untersuchung durchf{\"u}hren zu k{\"o}nnen, wurden alle n{\"o}tigen Bausteine (Protein-Erkennungssequenz zur Reaktion mit Nukleophil-Polymer und Polymer-Erkennungssequenz mit Nukleophil-Protein) hergestellt. Als Polymerisationstechnik wurde die radikalische Polymerisation mit reversibler Deaktivierung (im Detail, Atom Transfer Radical Polymerization, ATRP und Reversible Addition-Fragmentation Chain Transfer, RAFT polymerization) gew{\"a}hlt, um eine enge Molmassenverteilung zu erreichen. Die Herstellung der Bausteine begann mit der Synthese der Peptide via automatisierter Festphasen-Peptidsynthese, um eine einfache {\"A}nderung der Peptidsequenz zu gew{\"a}hrleisten und um eine Modifizierung der Polymerkette nach der Polymerisation zu umgehen. Um die ben{\"o}tigte unterschiedliche Funktionalit{\"a}t der zwei Peptidsequenzen (freier C-Terminus bei der Erkennungssequenz bzw. freier N-Terminus bei dem Nukleophil) zu erreichen, wurden verschiedene Linker zwischen Harz und Peptid verwendet. Danach wurde der Ketten{\"u}bertr{\"a}ger (chain transfer agent, CTA) zur Kontrolle der Polymerisation mit dem auf dem Harz befindlichen Peptid gekoppelt. Die f{\"u}r die anschließende Polymerisation verwendeten Monomere basierten auf Acrylamiden und Acrylaten und wurden anhand ihrer Eignung als Alternativen zu PEG ausgew{\"a}hlt. Es wurde eine k{\"u}rzlich entwickelte Technik basierend auf der RAFT-Polymerisation (xanthate-supported photo-iniferter RAFT, XPI-RAFT) verwendet um eine Reihe an Peptid-Polymeren mit unterschiedlichen Molekulargewichten und engen Molekulargewichtsverteilungen herzustellen. Nach Entfernung der Schutzgruppen der Peptid-Seitenketten wurden die Peptid-Polymere zun{\"a}chst genutzt, um mittels Sortase-vermittelter Ligation zwei Polymerketten zu einem Blockcopolymer zu verbinden. Unter Verwendung von Ni2+-Ionen in Kombination mit einer Verl{\"a}ngerung der Erkennungssequenz um ein Histidin zur Unterdr{\"u}ckung der R{\"u}ckreaktion konnte ein maximaler Umsatz von 70 \% erreicht werden. Dabei zeigte sich ein oberes Limit von durchschnittlich 100 Wiederholungseinheiten; die Ligation von l{\"a}ngeren Polymeren war nicht erfolgreich. Danach wurden ein Modellprotein und ein Nanobody mit vielversprechenden medizinischen Eigenschaften mit den f{\"u}r die enzymkatalysierte Ligation ben{\"o}tigten Peptidsequenzen f{\"u}r die Kopplung mit den zuvor hergestellten Peptid-Polymeren verwendet. Dabei konnte bei Verwendung des Modellproteins keine Bildung von Protein-Polymer-Konjugaten beobachtet werden. Der Nanobody konnte dagegen C-terminal mit einem Polymer funktionalisiert werden. Dabei wurde eine {\"a}hnliche Limitierung in der Polymer-Kettenl{\"a}nge beobachtet wie zuvor. Die auf Ni-Ionen basierte Strategie zur Gleichgewichtsverschiebung hatte hier keinen ausschlaggebenden Effekt, w{\"a}hrend die Verwendung von einem {\"U}berschuss an Polymer zur vollst{\"a}ndigen Umsetzung des Edukt-Nanobody f{\"u}hrte. Die erhaltenen Daten aus diesem Projekt bilden eine gute Basis f{\"u}r weitere Forschung in dem vielversprechenden Feld der enzymkatalysierten Herstellung von Protein-Polymer-Konjugaten und Blockcopolymeren. Langfristig k{\"o}nnte diese Herangehensweise eine vielseitig einsetzbare Herstellungsmethode von ortsspezifischen therapeutischen Protein-Polymer Konjugaten darstellen, welche sowohl eine hohe Aktivit{\"a}t als auch eine lange Zirkulationszeit im Blut aufweisen.},
  language  = {en}
}