Novel Antimicrobial Peptides with High Anticancer Activity and Selectivity

Abstract

We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

Human tear proteomics and peptidomics in ophthalmology: Toward the translation of proteomic biomarkers into clinical practice

“…The outer membranes of cancer cells carry more negatively charged molecules than normal cells. Thus, because of their amphipathic features, the antimicrobial peptides might bind cancer cells preferentially, inducing their death by necrosis or apoptosis (95). This suggests that the antimicrobial peptides (AMPs) could be good templates for the development of anticancer agents; several AMPs have been recognized as such (96).…”

Thaulin-1: The first antimicrobial peptide isolated from the skin of a Patagonian frog Pleurodema thaul (Anura: Leptodactylidae: Leiuperinae) with activity against Escherichia coli

“…AMPs are important functional molecules in the innate immune system and they play defensive roles against external risk factors. However, besides antimicrobial activity, multiple potential applications have been identified for AMPs such as anticancer [Oelkrug et al, 2015;Wu et al, 2014;Gaspar et al, 2013;Chu et al, 2015], insecticidal [Smith et A C C E P T E D M A N U S C R I P T 5 al., 2011], chemotactic [Craik et al, 2010] antioxidant [Guo et al, 2014], spermicidal [Zairi et al, 2009], wound healing [Mangoni et al 2016]; protease inhibition [Miller et al, 1989] and neuropeptide function [Pukala et al, 2006] among others. Moreover, even derivatives of AMPs have shown a broad range of different applications [Abdel-Wahab et al, 2008;Chalrabarti et al, 2003;Schulze et al, 2015].…”

Design and synthesis of a novel peptide for selective detection of cancer cells

“…Peptide 1 accumulates in the cytoplasm of cancer cells after penetrating through the cell membrane (Figures 5 and 6). Such cell‐penetrating peptides can be lethal to normal cells, especially at higher concentrations (Chu et al, 2015; Gaspar, Veiga, & Castanho, 2013). Therefore, the viability of normal and cancer cells was assessed by the MTT assay and using peptide concentrations up to 100 µM.…”