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MATPROG-Matprogrammet: Norsk mat fra sjø og land

Development of new antimicrobial agents: Structure-Function Analysis and Construction of Antimicrobial Peptides

Awarded: NOK 14.3 mill.

Antimicrobial peptides are produced by nearly all organisms - from bacteria to humans. These peptides may be developed into useful antimicrobial drugs and additives in food and animal feed. However, lack of insight into peptide-cell interactions and struc tural features (on peptides and target cells) that are important for the potency and specificity of antimcrobial peptides is a major hindrance for their optimal use, as well as for the development of new peptide variants with enhanced antimicrobial activi ty. The principal objective is to identify these interactions and structures, using (i) DNA microarray technology to compare sensitive and resistant target-cells and (ii) peptides that have very similar primary structures, but different specificities/pote ncies. Thus, the following questions will be addressed: · Why do very similar peptides show different potency and specificity with respect to the bacteria they kill? · Why do very similar bacteria display different sensitivity/resist To address these questions, the project will pursue the following sub-goals: - Identify regions, structures and or residues that are important specificity determinants in a set of antimicrobial peptides rminants in a - Identify regions, structures and or molecules (such as peptide receptors/docking sites on target-cells) that are important sensitivty determinants on bacteria - Identify in antimicrobial peptides regions, structures and or residues that are (directly or indirectly) specifically recognised by immuni ty proteins at are (directly or - Identify in immunity proteins regions, structures and or residues that are (directly or indirectly) specifically recognised by antimicrobial peptides - Use microarray technology to identify pathways and proteins that a re involved in the mode of action of antimicrobial peptides d in the New peptide variants will be constucted in order to identify regions, structures and or residues that are important specificity determinants, and structural analysis by NMR-spectroscopy, will be carried out in order to gain insight into the three-dimensional structure of regions relevant for potency and specificity

Funding scheme:

MATPROG-Matprogrammet: Norsk mat fra sjø og land