Lytic Peptides with Improved Stability and Selectivity Designed for Cancer Treatment

Chen, Long; Tu, Zhigang; Voloshchuk, Natalya; Liang, Jun

doi:10.1002/jps.23043

Cited by 27 publications

(87 citation statements)

References 28 publications

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“…Like other lytic peptides, PTP-7 has strong cytotoxicity to tissue cells by causing cell membrane lysis 15, 20 . Interestingly, peptide CL-1 demonstrated low cytotoxicity.…”

Section: Resultsmentioning

confidence: 99%

“…The electrostatic attraction of cationic peptides to the cell membranes is the PTP-7 CL-1 critical step which is solely determined by the net positive charges of a peptide. In addition, the folding of the peptide chain into a specific conformation, usually an alpha-helical structure, has proven to be a necessary and energy favorable process for peptide insertion into cell membranes 15 . By replacing two lysine residues with arginines, resulting peptide CL-1 had the same positive charges (+2) as PTP-7.…”

Section: Resultsmentioning

confidence: 99%

“…The cytotoxicity of peptides was determined using Thiazolyl Blue Tetrazolium Bromide (MTT) assay as described previously 15, 19 . Briefly, cells in complete medium were added into 96-well plates (5 × 10 3 cells/well) and cultured at 37 °C for 14–16 hours.…”

Section: Methodsmentioning

confidence: 99%

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Peptide Fibrils with Altered Stability, Activity, And Cell Selectivity

Chen

Liang

2013

Biomacromolecules

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Peptides have some unique and superior features compared to proteins. However, the use of peptides as therapeutics is hampered by their low stability and cell selectivity. In this study, a new lytic peptide (CL-1, FLGALFRALSRLL) was constructed. Under the physiological condition, peptide CL-1 self-assembled into dynamically stable aggregates with fibrils-like structures. Aggregated CL-1 demonstrated dramatically altered activity and stability in comparison with single molecule CL-1 and other lytic peptides: when incubated with co-cultured bacteria and tissue cells, CL-1 aggregates killed bacteria selectively but spared co-cultured human cells; CL-1 aggregates kept intact in human serum for more than five hours. Peptide-cell interaction studies performed on lipid monolayers and live human tissue cells revealed that in comparison with monomeric CL-1, aggregated CL-1 had decreased cell affinity and membrane insertion capability on tissue cells. A dynamic process involving aggregate dissociation and rearrangement seemed to be an essential step for membrane bound CL-1 aggregates to realize its cytotoxicity to tissue cells. Our study suggests that peptide aggregation could be as important as the charge and secondary structure of a peptide in affecting peptide-cell interactions. Controlling peptide self-assembly represents a new way to increase the stability and cell selectivity of bioactive peptides for wide biomedical applications.

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“…Like other lytic peptides, PTP-7 has strong cytotoxicity to tissue cells by causing cell membrane lysis 15, 20 . Interestingly, peptide CL-1 demonstrated low cytotoxicity.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Peptide Fibrils with Altered Stability, Activity, And Cell Selectivity

Chen

Liang

2013

Biomacromolecules

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“…The secondary structures of peptides were analyzed using CDPRO software based on the circular dichroism (CD) spectra of peptides recorded on a Jasco J-710 spectropolarimeter [15]. Peptide self-assembly in solution to form peptide aggregates was estimated by using 1-anilinonaphthalene-8-sulfonic acid (1, 8-ANS) as a fluorescence probe [15].…”

Section: Methodsmentioning

confidence: 99%

“…Peptide self-assembly in solution to form peptide aggregates was estimated by using 1-anilinonaphthalene-8-sulfonic acid (1, 8-ANS) as a fluorescence probe [15]. The ANS (20 μM) fluorescence emission spectrum changes associated with peptide aggregation were recorded on the fluorescence microplate reader (Biotek Inc.) by setting excitation wavelength at 369 nm.…”

Section: Methodsmentioning

confidence: 99%

Bacteria responsive antibacterial surfaces for indwelling device infections

Traba

Liang

2015

Journal of Controlled Release

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Indwelling device infections now represents life-threatening circumstances as a result of the biofilms’ tolerance to antibiotic treatments. Current antibiotic impregnation approaches through sustained antibiotic release have some unsolved problems which include short life-span, narrowed antibacterial spectrum, ineffectiveness towards resistant mutants, and the potential to hasten the antibiotic resistance process. In this study, bacteria responsive anti-biofilm surfaces were developed using bioactive peptides with proved activity to antibiotic resistant bacteria and biofilms. Resulting surfaces were stable under physiological conditions and in the presence of high concentrations of salts (0.5 M NaCl) and biomacromolcules (1.0% DNA and 2.0% alginate), and thus showed good biocompatibility to various tissue cells. However, lytic peptide immobilized surfaces could sense bacteria adhesion and kill attached bacteria effectively and specifically, so biofilms were unable to develop on the lytic peptide immobilized surfaces. Bacteria responsive catheters remained biofilm free for up to a week. Therefore, the bacteria responsive antibacterial surfaces developed in this study represent new opportunities for indwelling device infections.

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Visible‐Light Microscopic Discovery of Up to 150 μm Long Helical Amyloid Fibrils Built of the Dodecapeptide H‐(Val‐Ala‐Leu)₄‐OH and of Decapeptides Derived from Insulin

Swiontek

Kamiński

Kolesińska

et al. 2016

Chemistry & Biodiversity

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In the formation of amyloid fibrils from small peptides, the appearance of superhelices of (P)- or (M)-helicity has been observed for the first time; high concentrations of the peptides and extended periods of incubation at physiological pH appear to be important for this phenomenon. In view of the general importance of peptide and protein aggregation, we give a brief overview with selected examples for demonstration.

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Lytic Peptides with Improved Stability and Selectivity Designed for Cancer Treatment

Cited by 27 publications

References 28 publications

Peptide Fibrils with Altered Stability, Activity, And Cell Selectivity

Peptide Fibrils with Altered Stability, Activity, And Cell Selectivity

Bacteria responsive antibacterial surfaces for indwelling device infections

Visible‐Light Microscopic Discovery of Up to 150 μm Long Helical Amyloid Fibrils Built of the Dodecapeptide H‐(Val‐Ala‐Leu)₄‐OH and of Decapeptides Derived from Insulin

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Lytic Peptides with Improved Stability and Selectivity Designed for Cancer Treatment

Cited by 27 publications

References 28 publications

Peptide Fibrils with Altered Stability, Activity, And Cell Selectivity

Peptide Fibrils with Altered Stability, Activity, And Cell Selectivity

Bacteria responsive antibacterial surfaces for indwelling device infections

Visible‐Light Microscopic Discovery of Up to 150 μm Long Helical Amyloid Fibrils Built of the Dodecapeptide H‐(Val‐Ala‐Leu)4‐OH and of Decapeptides Derived from Insulin

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Visible‐Light Microscopic Discovery of Up to 150 μm Long Helical Amyloid Fibrils Built of the Dodecapeptide H‐(Val‐Ala‐Leu)₄‐OH and of Decapeptides Derived from Insulin