Universität zu Köln

Drexelius, Marco Gerry ORCID: 0000-0002-5813-2116 (2023). Development and application of antimicrobial peptides based on sC18 to fight antibiotic resistance and bacterial adhesion. PhD thesis, Universität zu Köln.

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Abstract

Bacteria remain one of the most concerning medical threats to humanity, causing millions of deaths each year. Even after almost a century of antibiotic development, further research is required to combat the growing number of bacterial resistances to common antibiotics and the formation of biofilms on medical equipment. In the last decades, antimicrobial peptides have emerged as promising candidates to offer a solution to both problems owing to their ability to lyse the bacterial membranes selectively, without harming host tissues. In this work, the antimicrobial activity of the recently developed cell-penetrating peptide sC18 (GLRKRLRKFRNKIKEK) should be increased by modulating its amino acid sequence. Overall, three approaches were used to design novel antimicrobial peptides and these were tested for antibiotic activity against a range of bacteria. At first, specific substitutions with phenylalanine and fluorinated phenylalanine were utilized to modify the physicochemical properties and develop peptides with high antimicrobial activity combined with selectivity towards mammalian cells. These peptides were further investigated for their proteolytic stability and membrane disruptive mechanism. Furthermore, new sets of antimicrobial peptides were designed using a rational approach introducing cationic and hydrophobic amino acid substitutions to enhance their overall antibacterial activity without haemolytic side effects. With these peptides the influence of peptide length and the specific substitution positions were investigated. Based on the most promising variant, chimeric peptides were designed and immobilized onto solid titanium surfaces to prevent the adhesion of bacteria and further biofilm formation.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Drexelius, Marco Gerry marco_drexelius@web.de orcid.org/0000-0002-5813-2116 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-647930
Date:	7 February 2023
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	Chemistry and allied sciences Life sciences
Uncontrolled Keywords:	Keywords Language Antimicrobial peptides English Drug development English Multiresistant bacteria targetting English Surface modification English
Date of oral exam:	2 December 2022
Referee:	Name Academic Title Neundorf, Ines Prof. Dr. Baumann, Ulrich Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/64793