Synthesis and antibacterial study of cell-penetrating peptide conjugated trifluoroacetyl and thioacetyl lysine modified peptides.

Substrate-based sirtuin inhibitors target bacterial genome and RNA and provide a promising approach to address bacterial resistance issues, if cellular internalisation can be achieved. We designed N-trifluoroacetyl lysine and N-thioacetyl lysine peptides (KP 13, KP 15 and KP 24) as inhibitors of bacterial sirtuins and their cell-penetrating peptide conjugates Tat KP 13, Tat KP 15 and Tat KP 24. The conjugated peptides were successfully internalised and showed signs of bacterial transcription inhibition resulting in enhanced antibacterial potency against model Gram negative and Gram positive pathogens.

Novel Cell-Penetrating Peptide Conjugated Proteasome Inhibitors: Anticancer and Antifungal Investigations.

Cell-penetrating peptide conjugated peptide aldehydes and showed low micromolar anticancer and antifungal activities and synergistic action in combination with cisplatin and amphotericin B against cancer and fungal cells, respectively. and were significantly more potent than Ixazomib in inhibiting the human 20S proteasomes with IC values in the low nanomolar range. Treatment with and caused membrane disruption and pore formation in HeLa and BE(2)-C cells and inhibition and eradication of biofilms.