Anticandidal Activity of Lipopeptides Containing an LL-37-Derived Peptide Fragment KR12.

Candidiasis belongs to common fungal infections and is usually mild and self-limiting. However, in patients with immunodeficiencies, it can transform into invasive infections with high mortality. Long-term antifungal treatment can lead to the emergence of resistance. The problem is further complicated by the development of fungal biofilm resistant to conventional antimicrobials. Due to a limited choice of available antifungals, the development of novel active agents, such as antimicrobial peptides (AMPs), is highly desirable. Human cathelicidin LL-37 is an intensively studied AMP with a confirmed broad spectrum of antimicrobial activities. Due to the relatively high costs of production, the design of shorter analogs of LL-37 has been recommended. In this study, we synthesized a KR12 amide, KRIVQRIKDFLR-NH, and its 24 derivatives obtained by substitution with fatty acids. The compounds were tested for their antifungal potential. They exhibited activity against the , , and . Five compounds: C-KR12-NH, C-KR12-NH, C-KR12-NH, 2-butyloctanoic acid-KR12-NH, and 4-phenylbenzoic acid-KR12-NH were highly active against planktonic cells. C-KR12-NH demonstrated also activity against biofilm cultured on polystyrene for 24, 48 and 72 h. Lipidation has proven to be an effective strategy for improving microbiological activity of the KR12-NH peptide.