Antimikrobielle Peptide Dissertation

I have never thought that a 5-page research can be done in less than 6 hours.Thanks to Speedy Paper I managed to kick my professor's butt and party all the night.In recent years, the rapid increase of antibiotic resistances and the expansion of multi-resistant bacterial strains have provoked the need to develop novel antibiotics.

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Ihr einzigartiger Wirkmechanismus und das seltene Aufkommen von Resistenzen, machen AMPs interessant für die Pharmazie.

AMPs sind aktiv gegen unterschiedlichste Mikroorganismen u.a.

The present thesis focuses on improving the antimicrobial activity of AMPs by using different strategies like synthesis of AMP-conjugates, membrane immobilization of AMPs, and amino acid exchanges within the AMP sequence.

For this, multiple imidazolium-salts, already described as antibacterial agents, were conjugated to AMPs via solid phase peptide synthesis, developing a branched conjugate.

Both immobilization techniques were successfully performed, still showing a high antimicrobial activity of the immobilized compound.

The cell-penetrating peptide s C18 was converted to an AMP by amino acid exchanges with isoleucine and phenylalanine.Eine der neuen Verbindungen, IL-KKA (3a), zeigte die höchste Selektivität und kann als Leitstruktur für die Entwicklung von neuen Antibiotika verwendet werden.80% der heutigen Infektionen werden durch Biofilme verursacht.gram-positive und gram-negative Bakterien sowie Pilze, Viren und Parasiten.In dieser Arbeit soll die antimikrobielle Aktivität von AMPs durch Herstellung von AMP-Konjugaten, Membranimmobilisierung von AMPs und den Austausch von Aminosäuren innerhalb der AMP Sequenz weiter erhöht werden.Isoleucine and phenylalanine mono mutants already exhibited an increased activity against a wide spectrum of bacteria.A higher amount of phenylalanine in the sequence leads to a further increased antimicrobial activity.The insertion of hydrophobic amino acids at position 10 led to the formation of a characteristic α-helix, while the positions 15 and 16 seemed to be necessary for hydrophobic membrane interactions.All in all, this thesis highlights the successful modification of AMPs to more active antimicrobial agents, which make them extremely interesting for the design of future antibiotics and the application of potential anti-biofilm agents.Unterschiedlich modifizierte Imidazoliumsalze, die bereits für ihre antimikrobielle Aktivität bekannt sind, wurden mit Hilfe der Festphasenpeptidsynthese an AMPs gekuppelt.Die Kombination der beiden Komponenten zeigte eine höhere Aktivität gegen multiresistente Bakterien.


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