| Abstract: | The development of novel solutions to fight microbial food contaminants rests upon two pillars, which are the development of resistant strains and consumers' desire for a reduced consumption of synthetic drugs. Natural antimicrobial peptides possess the qualities to overcome these issues. De novo synthesis of novel antifungal compounds is a major progress that has been facilitated by the identification of parameters involved in the antimicrobial activity. A 14‐residue peptide named KK14, with the sequence KKFFRAWWAPRFLK‐NH2, was designed and inhibited conidial germination and fungal growth of food contaminants within the range 6.25 to 50 μg/ml and 6.25 to 100 μg/ml, respectively. The study of three analogues of the peptide highlighted the role of some residues in the structural conformation of the peptide and its antifungal activity. The substitution of a Pro residue with Arg increased the helical content of the peptide not only its antifungal activity but also its cytotoxicity. The insertion of an unnatural bulky residue β‐diphenylalanine or a full d ‐enantiomerization overall increased the antifungal potency. The four peptides showed similar behaviour towards salt increase, heat treatment, and pH decrease. Interestingly, the d enantiomer remained the most active at high pH and after proteolytic digestion. The four peptides did not present haemolytic activity up to 200 μg/ml but had different behaviours of cytotoxicity. These differences could be crucial for potential application as pharmaceutical or food preservatives. |
