Non-natural amino acids into LfcinB-derived peptides: effect in their (i) proteolytic degradation and (ii) cytotoxic activity against cancer cells.

The dimeric peptide [F]: (RRWQWRKKLG)-K-Ahx has exhibited a potent cytotoxic effect against breast cancer cell lines, with position 26 (F) being the most relevant for anti-cancer activity. In this investigation, six analogues of the [F] peptide were synthesized in which the 26th position was replaced by non-natural hydrophobic amino acids, finding that some modifications increased the resistance to proteolytic degradation exerted by trypsin or pepsin. Additionally, these modifications increased the cytotoxic effect against breast cancer cells and generated cell death mediated by apoptosis pathways, activating caspases 8 and 9, and did not compromise the integrity of the cytoplasmic membrane.

Short peptides conjugated to non-peptidic motifs exhibit antibacterial activity.

Short peptides derived from buforin and lactoferricin B were conjugated with other antimicrobial molecules of different chemical natures. The sequences RLLR, RLLRLLR, RWQWRWQWR, and RRWQWR were conjugated at their N-terminal end with non-peptidic molecules such as 6-aminohexanoic acid, ferrocene, caffeic acid, ferulic acid, and oxolinic acid. Peptide conjugates and unmodified peptides were synthesized by means of solid-phase peptide synthesis using the Fmoc/Bu strategy (SPPS-Fmoc/Bu), purified RP-SPE, and characterized RP-HPLC and MS.