A cationic amphiphilic peptide ABP-CM4 exhibits selective cytotoxicity against leukemia cells

Genetically engineered protein polymers functionalized with bioactive domains offer potential as multifunctional versatile materials for biomedical use. The present work describes the fabrication and characterization of antimicrobial fibre mats comprising the antimicrobial elastin-like recombinamer CM4-A200. The CM4-A200 protein polymer derives from the genetic fusion of the ABP-CM4 antimicrobial peptide from Bombyx mori with 200 repetitions of the pentamer VPAVG. This is the first report on non-crosslinked fibre mats fabricated with an antimicrobial elastin-like recombinamer stable in solution.Thermal gravimetric analysis of CM4-A200 fibre mats shows one single degradation step at temperatures above 300 ºC, with fibres displaying a higher thermal degradation activation. The electrospun CM4-A200 fibres display high antimicrobial activity against Gram-positive and Gram-negative bacteria with no detectable cytotoxic effects against normal human skin fibroblasts and keratinocytes, revealing the great potential of these polymers for the fabrication of biomedical materials.

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“…Finally, a chemically synthesized ABP-CM4 did not display haemolytic activity in fresh human red blood cells [55].…”

Section: Discussionmentioning

confidence: 92%

Single step fabrication of antimicrobial fibre mats from a bioengineered protein-based polymer

et al. 2017

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“…Subsequently, we synthesized ABP-CM4 using the plasmid of pET-32a, with T7 promoter and thioredoxin (TrxA) as a Fig. Adopted from Chen et al (2010). a Secondary structure analysis of ABP-CM4 by CD spectroscopy.…”

Section: Expression Of Abp-cm4 In Escherichia Colimentioning

confidence: 99%

The antibacterial peptide ABP-CM4: the current state of its production and applications

Zhang

et al. 2011

Amino Acids

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The increasing resistance of bacteria and fungi to currently available antibiotics is a major concern worldwide, leading to enormous efforts to develop new antibiotics with new modes of actions. Antibacterial peptide CM4 (ABP-CM4) is a small cationic peptide with broad-spectrum activities against bacteria, fungi, and tumor cells, which may possibly be used as a promising candidate for a new antibiotic. For pharmaceutical applications, a large quantity of antimicrobial peptides needs to be produced economically. In this communication, the progress in the structural characteristics, heterologous production, and biological evaluation of ABP-CM4 are reviewed.

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“…A peptide ABP-CM4 isolated from the Chinese silkworm has been found to kill the leukemia cells K562, U937, and THP-1 through only disrupting the cell membrane and without penetrating into the cells. 32 However, a hybrid peptide P18 is known to kill the human melanoma cells not only through disrupting the cell membrane but also inducing the necrosis process. 33 …”

Section: Discussionmentioning

confidence: 99%

Anti-proliferative effect on a colon adenocarcinoma cell line exerted by a membrane disrupting antimicrobial peptide KL15

Chen

Tsai

et al. 2015

Cancer Biology & Therapy

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Abbreviations: ABC, ATB-binding cassette; HPK, histidine protein kinase; HNSCC, head and neck squamous cell carcinoma; HFFF, human foetal foreskin fibroblast; PS, phospholipid phosphatidylyserine; TFE, 2,2,2-trifluoroethanol; MTT, 3-(4 5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide.The antimicrobial and anticancer activities of an antimicrobial peptide (AMP) KL15 obtained through in silico modification on the sequences of 2 previously identified bacteriocins m2163 and m2386 from Lactobacillus casei ATCC 334 by us have been studied. While significant bactericidal effect on the pathogenic bacteria Listeria, Escherichia, Bacillus, Staphylococcus, Enterococcus is exerted by KL15, the AMP can also kill 2 human adenocarcinoma cells SW480 and Caco-2 with measured IC 50 as 50 mg/ml or 26.3 mM. However, the IC 50 determined for KL15 on killing the normal human mammary epithelial cell H184B5F5/M10 is 150 mg/ml. The conformation of KL15 dissolved in 50% 2,2,2-trifluroroethanol or in 2 large unilamellar vesicle systems determined by circular dichroism spectroscopy appears to be helical. Further, the cell membrane permeability of treated SW480 cells by KL15 appears to be significantly enhanced as studied by both flow cytometry and confocal microscopy. As observed under a scanning electron microscope, the morphology of treated SW480 cells is also significantly changed as treating time by 80 mg/ml KL15 is increased. KL15 appears to be able to pierce the cell membrane of treated SW480 cells so that numerous porous structures are generated and observable. Therefore, KL15 is likely to kill the treated SW480 cells through the necrotic pathway similar to some recently identified AMPs by others.

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A cationic amphiphilic peptide ABP-CM4 exhibits selective cytotoxicity against leukemia cells

Cited by 43 publications

References 30 publications

Single step fabrication of antimicrobial fibre mats from a bioengineered protein-based polymer

Single step fabrication of antimicrobial fibre mats from a bioengineered protein-based polymer

The antibacterial peptide ABP-CM4: the current state of its production and applications

Anti-proliferative effect on a colon adenocarcinoma cell line exerted by a membrane disrupting antimicrobial peptide KL15

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