Synthesis and evaluation of lysozyme derivatives exhibiting an enhanced antimicrobial action.
In order to generate novel preservatives exhibiting a broad antimicrobial spectrum against Gram-positive as well as Gram-negative bacteria, lysozyme was modified by the covalent attachment of caffeic acid and cinnamic acid, respectively. Linkage of these organic acids to lysozyme was achieved by the constitution of amide bindings between the carboxyl group of ligands and primary amino groups of the enzyme mediated by a carbodiimide. Compared to nonmodified lysozyme, the lytic activity of all resulting conjugates was reduced. In contrast, bacterial growth of Escherichia coli (ATCC 8739) could be strongly inhibited by lysozyme-caffeic acid conjugates and to a lower degree also by lysozyme-cinnamic acid conjugates. The minimal inhibitory concentration against E. coli was 0.05% for the lysozyme derivative of the highest antimicrobial activity. However, the efficacy of lysozyme derivatives against Staphylococcus aureus (ATCC 6538) was slightly reduced. As the antimicrobial spectrum of lysozyme altogether could be substantially widened, these derivatives represent promising candidates as novel preservatives for various pharmaceutical and cosmetic formulations.
Bernkop-Schnürch
A
A
Center of Pharmacy, Institute of Pharmaceutical Technology, University of Vienna, Althanstr. 14, A-1090 Vienna, Austria. andreas.bernkop-schnuerch@univie.ac.at
Krist
S
S
Vehabovic
M
M
Valenta
C
C
D000596:Amino Acids / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology; D004800:Enzymes, Immobilized; D004926:Escherichia coli / Q000187:drug effects; D008024:Ligands; D008826:Microbial Sensitivity Tests; D008837:Micrococcus / Q000187:drug effects; D009113:Muramidase / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000890:Anti-Infective Agents; D002109:Caffeic Acids; D002934:Cinnamates; D004800:Enzymes, Immobilized; D008024:Ligands; C029010:cinnamic acid; D009113:Muramidase; C040048:caffeic acid