Antimicrobial peptides (AMPs) have emerged as a promising therapeutic scaffold for combating antibiotic-resistant infections and cancer. Aurein 1.2, the most studied peptide in the aurein family, displays a broad spectrum of bi-functionality against bacterial and cancer cells, making it one of the smallest active amphibian peptides reported to date. The phenylalanine residues at positions 3 and 13 are critical for biological activity because they serve as essential anchors for membrane binding. In this study, a series of new analogues of aurein 1.2 containing fluorinated phenylalanine were synthesized by solid-phase peptide synthesis (SPPS), Fmoc-(9-fluorenylmethoxycarbonyl) chemistry, purified by High Performance Liquid Chromatography (HPLC), analysed by mass spectrometry (MS). The antiproliferative activity was determined in normal and tumour cell lines (MCF-12F, MCF-7, MDA-MB-231, U87 and MG63 cells) by MTT dye reduction assay. The target compounds exhibited different concentration-dependent antiproliferative effect against the tumour cell lines after 72 h treatment. The highest antiproliferative activity was observed with the peptide EH [Phe (4-F)]3,13[Lys]4 (IC50 = 9.79 ± 0.96 µM) in U87 cells and (IC50 = 9.96 ± 0.8 µM) in MG63 cells. Significant selectivity (SI > 2) was observed for the peptide analogue EH [Phe (4-F)]3 in MCF-7 cells (SI = 2.08).Antimicrobial activity was assessed against Gram-positive and Gram-negative bacteria. The aurein 1.2 and its analogues possessed better antibacterial activity against Gram-positive bacteria than Gram-negative bacteria. The obtained results reveal that replacement of Phe with Phe(4-F) and Asp with Lys can increase both the potency and activity. The best results were obtained with the peptide EH [Phe(4-F)]3,13[Lys]4 (MIC = 10 µg/ml), against S. aureus 3703. However, compared to the antibacterial data of the positive controls, the results showed weaker antibacterial activity.
Design, synthesis, and biological analysis of aurein 1.2 analogues incorporating fluorinated phenylalanine
Montesi M.;Panseri S.;
2026
Abstract
Antimicrobial peptides (AMPs) have emerged as a promising therapeutic scaffold for combating antibiotic-resistant infections and cancer. Aurein 1.2, the most studied peptide in the aurein family, displays a broad spectrum of bi-functionality against bacterial and cancer cells, making it one of the smallest active amphibian peptides reported to date. The phenylalanine residues at positions 3 and 13 are critical for biological activity because they serve as essential anchors for membrane binding. In this study, a series of new analogues of aurein 1.2 containing fluorinated phenylalanine were synthesized by solid-phase peptide synthesis (SPPS), Fmoc-(9-fluorenylmethoxycarbonyl) chemistry, purified by High Performance Liquid Chromatography (HPLC), analysed by mass spectrometry (MS). The antiproliferative activity was determined in normal and tumour cell lines (MCF-12F, MCF-7, MDA-MB-231, U87 and MG63 cells) by MTT dye reduction assay. The target compounds exhibited different concentration-dependent antiproliferative effect against the tumour cell lines after 72 h treatment. The highest antiproliferative activity was observed with the peptide EH [Phe (4-F)]3,13[Lys]4 (IC50 = 9.79 ± 0.96 µM) in U87 cells and (IC50 = 9.96 ± 0.8 µM) in MG63 cells. Significant selectivity (SI > 2) was observed for the peptide analogue EH [Phe (4-F)]3 in MCF-7 cells (SI = 2.08).Antimicrobial activity was assessed against Gram-positive and Gram-negative bacteria. The aurein 1.2 and its analogues possessed better antibacterial activity against Gram-positive bacteria than Gram-negative bacteria. The obtained results reveal that replacement of Phe with Phe(4-F) and Asp with Lys can increase both the potency and activity. The best results were obtained with the peptide EH [Phe(4-F)]3,13[Lys]4 (MIC = 10 µg/ml), against S. aureus 3703. However, compared to the antibacterial data of the positive controls, the results showed weaker antibacterial activity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
