@phdthesis{Maltseva2005,
  author    = {Maltseva, Elena},
  title     = {Model membrane interactions with ions and peptides at the air/water interface},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-5670},
  school      = {Universit{\"a}t Potsdam},
  year      = {2005},
  abstract  = {The interactions between peptides and lipids are of fundamental importance in the functioning of numerous membrane-mediated biochemical processes including antimicrobial peptide action, hormone-receptor interactions, drug bioavailability across the blood-brain barrier and viral fusion processes. Alteration of peptide structure could be a cause of many diseases. Biological membranes are complex systems, therefore simplified models may be introduced in order to understand processes occurring in nature. The lipid monolayers at the air/water interface are suitable model systems to mimic biological membranes since many parameters can be easily controlled. In the present work the lipid monolayers were used as a model membrane and their interactions with two different peptides B18 and Amyloid beta (1-40) peptide were investigated. B18 is a synthetic peptide that binds to lipid membranes that leads to the membrane fusion. It was demonstrated that it adopts different structures in the aqueous solutions and in the membrane interior. It is unstructured in solutions and forms alpha-helix at the air/water interface or in the membrane bound state. The peptide has affinity to the negatively charged lipids and even can fold into beta-sheet structure in the vicinity of charged membranes at high peptide to lipid ratio. It was elucidated that in the absence of electrostatic interactions B18 does not influence on the lipid structure, whereas it provides partial liquidization of the negatively charged lipids. The understanding of mechanism of the peptide action in model system may help to develop the new type of antimicrobial peptides as well as it can shed light on the general mechanisms of peptide/membrane binding. The other studied peptide - Amyloid beta (1-40) peptide, which is the major component of amyloid plaques found in the brain of patients with Alzheimer's disease. Normally the peptide is soluble and is not toxic. During aging or as a result of the disease it aggregates and shows a pronounced neurotoxicity. The peptide aggregation involves the conformational transition from a random coil or alpha-helix to beta-sheets. Recently it was demonstrated that the membrane can play a crucial role for the peptide aggregation and even more the peptide can cause the change in the cell membranes that leads to a neuron death. In the present studies the structure of the membrane bound Amyloid beta peptide was elucidated. It was found that the peptide adopts the beta-sheet structure at the air/water interface or being adsorbed on lipid monolayers, while it can form alpha-helical structure in the presence of the negatively charged vesicles. The difference between the monolayer system and the bulk system with vesicles is the peptide to lipid ratio. The peptide adopts the helical structure at low peptide to lipid ratio and folds into beta-sheet at high ratio. Apparently, Abeta peptide accumulation in the brain is concentration driven. Increasing concentration leads to a change in the lipid to peptide ratio that induces the beta-sheet formation. The negatively charged lipids can act as seeds in the plaque formation, the peptide accumulates on the membrane and when the peptide to lipid ratio increases it the peptide forms toxic beta-sheet containing aggregates.},
  subject      = {Lipide},
  language  = {en}
}
@phdthesis{Hahn2009,
  author    = {Hahn, Harald},
  title     = {Modularer Ansatz zu multifunktionellen Polymer-Peptid-Fasern},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-33016},
  school      = {Universit{\"a}t Potsdam},
  year      = {2009},
  abstract  = {Die Kombination von Polymeren mit Peptiden vereint die Eigenschaften beider Stoffklassen miteinander. Dabei k{\"o}nnen 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 B{\"a}ndern anordnet. Die treibende Kraft f{\"u}r diesen Prozess ist die Anordnung des Peptidteils zu β-Faltblattstrukturen. Das Polymer-Peptid-Aggregat besitzt einen Peptidkern mit funktionalen Oberfl{\"a}chen, der lateral von einer Polyethylenoxidschale umgeben ist. Durch {\"A}nderung der Peptidsequenz war es bisher m{\"o}glich, die Eigenschaften dieser Fasern zu variieren. In der Arbeit wird ein modularer Ansatz zur vielf{\"a}ltigen Modifizierung einer Polymer-Peptid-Faser entwickelt. So ist es m{\"o}glich, die Eigenschaften der Fasern einzustellen, ohne die strukturbildende β-Faltblattsequenz ver{\"a}ndern zu m{\"u}ssen. 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 L{\"o}sungsmitteln unter hohen Ausbeuten durchf{\"u}hrbar. Im Rahmen der Arbeit wird die Erzeugung von Aziden untersucht und auf die Polymer-Peptid-Fasern {\"u}bertragen. Der Diazotransfer stellte dabei die Methode der Wahl dar, so k{\"o}nnen Azidgruppen aus Aminen gewonnen werden. Unter Verwendung der 1,3-dipolaren Addition konnten verschiedene alkinfunktionale Molek{\"u}le 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 Molek{\"u}le modifiziert. Diese Fasern konnten weiter genutzt werden, um Kalzium zu binden. Dabei variierte die Anzahl der gebundenen Kalziumionen in Abh{\"a}ngigkeit der jeweiligen Fasermodifikation erheblich. Weitere Untersuchungen, die Morphologie von Kalziumcarbonatkristallen betreffend, werden aktuell durchgef{\"u}hrt. 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 k{\"o}nnen in nachfolgenden Arbeiten so Silberdr{\"a}hte in Nanogr{\"o}ße erzeugt werden. An die azidfunktionalen Fasern k{\"o}nnen weitere funktionale Molek{\"u}le angebracht werden, um die Eigenschaften und das Anwendungsspektrum der Polymer-Peptid-Fasern zu erweitern.},
  language  = {de}
}
@phdthesis{Federico2011,
  author    = {Federico, Stefania},
  title     = {Synthetic peptides derived from decorin as building blocks for biomaterials based on supramolecular interactions},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-59661},
  school      = {Universit{\"a}t Potsdam},
  year      = {2011},
  abstract  = {In this work, the development of a new molecular building block, based on synthetic peptides derived from decorin, is presented. These peptides represent a promising basis for the design of polymer-based biomaterials that mimic the ECM on a molecular level and exploit specific biological recognition for technical applications. Multiple sequence alignments of the internal repeats of decorin that formed the inner and outer surface of the arch-shaped protein were used to develop consensus sequences. These sequences contained conserved sequence motifs that are likely to be related to structural and functional features of the protein. Peptides representative for the consensus sequences were synthesized by microwave-assisted solid phase peptide synthesis and purified by RP-HPLC, with purities higher than 95 mol\%. After confirming the desired masses by MALDI-TOF-MS, the primary structure of each peptide was investigated by 1H and 2D NMR, from which a full assignment of the chemical shifts was obtained. The characterization of the peptides conformation in solution was performed by CD spectroscopy, which demonstrated that using TFE, the peptides from the outer surface of decorin show a high propensity to fold into helical structures as observed in the original protein. To the contrary, the peptides from the inner surface did not show propensity to form stable secondary structure. The investigation of the binding capability of the peptides to Collagen I was performed by surface plasmon resonance analyses, from which all but one of the peptides representing the inner surface of decorin showed binding affinity to collagen with values of dissociation constant between 2•10-7 M and 2.3•10-4 M. On the other hand, the peptides representative for the outer surface of decorin did not show any significant interaction to collagen. This information was then used to develop experimental demonstration for the binding capabilities of the peptides from the inner surface of decorin to collagen even when used in more complicated situations close to possible appications. With this purpose, the peptide (LRELHLNNN) which showed the highest binding affinity to collagen (2•10-7 M) was functionalized with an N-terminal triple bond in order to obtain a peptide dimer via copper(I)-catalyzed cycloaddition reaction with 4,4'-diazidostilbene-2,2'-disulfonic acid. Rheological measurements showed that the presence of the peptide dimer was able to enhance the elastic modulus (G') of a collagen gel from ~ 600 Pa (collagen alone) to ~ 2700 Pa (collagen and peptide dimer). Moreover, it was shown that the mechanical properties of a collagen gel can be tailored by using different molar ratios of peptide dimer respect to collagen. The same peptide, functionalized with the triple bond, was used to obtain a peptide-dye conjugate by coupling it with N-(5'-azidopentanoyl)-5-aminofluorescein. An aqueous solution (5 vol\% methanol) of the peptide dye conjugate was injected into a collagen and a hyaluronic acid (HA) gel and images of fluorescence detection showed that the diffusion of the peptide was slower in the collagen gel compared to the HA gel. The third experimental demonstration was gained using the peptide (LSELRLHNN) which showed the lower binding affinity (2.3•10-4 M) to collagen. This peptide was grafted to hyaluronic acid via EDC-chemistry, with a degree of functionalization of 7 ± 2 mol\% as calculated by 1H-NMR. The grafting was further confirmed by FTIR and TGA measurements, which showed that the onset of decomposition for the HA-g-peptide decreased by 10 °C compared to the native HA. Rheological measurements showed that the elastic modulus of a system based on collagen and HA-g-peptide increased by almost two order of magnitude (G' = 200 Pa) compared to a system based on collagen and HA (G' = 0.9 Pa). Overall, this study showed that the synthetic peptides, which were identified from decorin, can be applied as potential building blocks for biomimetic materials that function via biological recognition.},
  language  = {en}
}