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Synthesis and Evaluation of Biological Activity of Antimicrobial--Pro-Proliferative Peptide Conjugates.

Kosikowska P, Pikula M, Langa P, Trzonkowski P, Obuchowski M, Lesner A - PLoS ONE (2015)

Bottom Line: Herein, we present the initial results of our studies aimed at the design of bifunctional peptide-based compounds.The chemical approach, that was utilized in this work, was based on the conjugation of antimicrobial peptides with the peptides, that have potential pro-proliferative and/or cytoprotective activity towards human keratinocytes and fibroblasts, in order to obtain antimicrobials with reduced cytotoxicity or compounds that maintain both activities, i.e. inhibit bacterial or fungi growth and activate cell proliferation/migration in in vitro tests.As a result, we obtained a group of peptide conjugates that effectively inhibited the growth of selected bacterial and fungi strains and were able to stimulate proliferation and migration of keratinocytes and fibroblasts under their effective microbicidal concentrations.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Chemistry, University of Gdansk, Gdansk, Poland.

ABSTRACT
Skin represents the largest organ of the human body and plays a crucial role in its protection from the negative impact of the outside environment, maintains its homeostasis, enables sensory interaction and thermoregulation. The traumatized skin tissue undergoes several phenotype switches due to progressive reoxygenation and release of cytokine and growth factors, that activate mechanisms of reparative processes. However, in case of wounds colonized with pathogenic microflora natural regenerative mechanisms become substantially impaired, that could lead to chronic inflammatory states with non-healing skin lesions. Herein, we present the initial results of our studies aimed at the design of bifunctional peptide-based compounds. The chemical approach, that was utilized in this work, was based on the conjugation of antimicrobial peptides with the peptides, that have potential pro-proliferative and/or cytoprotective activity towards human keratinocytes and fibroblasts, in order to obtain antimicrobials with reduced cytotoxicity or compounds that maintain both activities, i.e. inhibit bacterial or fungi growth and activate cell proliferation/migration in in vitro tests. As a result, we obtained a group of peptide conjugates that effectively inhibited the growth of selected bacterial and fungi strains and were able to stimulate proliferation and migration of keratinocytes and fibroblasts under their effective microbicidal concentrations.

No MeSH data available.


Related in: MedlinePlus

Pro-proliferative activity of the tested peptides towards human keratinocytes (A) and fibroblasts (B).Cells were incubated for 72 hours in serum-free DMEM medium in the presence of peptides applied at concentrations of 1,10, 25 and 50 μg/mL, respectively. The data represents results of MTT assay expressed as the percentage of the cell viability in comparison to their control sample (cells incubated in serum-free DMEM without tested peptides), additional positive control corresponds to the cells incubated in the presence of 10% FCS. All experiments were performed independently in triplicate. *P < 0.05, **P < 0.01, ***P < 0.001 vs. control.
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pone.0140377.g001: Pro-proliferative activity of the tested peptides towards human keratinocytes (A) and fibroblasts (B).Cells were incubated for 72 hours in serum-free DMEM medium in the presence of peptides applied at concentrations of 1,10, 25 and 50 μg/mL, respectively. The data represents results of MTT assay expressed as the percentage of the cell viability in comparison to their control sample (cells incubated in serum-free DMEM without tested peptides), additional positive control corresponds to the cells incubated in the presence of 10% FCS. All experiments were performed independently in triplicate. *P < 0.05, **P < 0.01, ***P < 0.001 vs. control.

Mentions: Pro-proliferative properties of the tested compounds was analyzed towards immortal human keratinocyte cell line (HaCaT) and fibroblasts obtained from healthy human skin biopsies (Fig 1A and 1B). [17,18].


Synthesis and Evaluation of Biological Activity of Antimicrobial--Pro-Proliferative Peptide Conjugates.

Kosikowska P, Pikula M, Langa P, Trzonkowski P, Obuchowski M, Lesner A - PLoS ONE (2015)

Pro-proliferative activity of the tested peptides towards human keratinocytes (A) and fibroblasts (B).Cells were incubated for 72 hours in serum-free DMEM medium in the presence of peptides applied at concentrations of 1,10, 25 and 50 μg/mL, respectively. The data represents results of MTT assay expressed as the percentage of the cell viability in comparison to their control sample (cells incubated in serum-free DMEM without tested peptides), additional positive control corresponds to the cells incubated in the presence of 10% FCS. All experiments were performed independently in triplicate. *P < 0.05, **P < 0.01, ***P < 0.001 vs. control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608580&req=5

pone.0140377.g001: Pro-proliferative activity of the tested peptides towards human keratinocytes (A) and fibroblasts (B).Cells were incubated for 72 hours in serum-free DMEM medium in the presence of peptides applied at concentrations of 1,10, 25 and 50 μg/mL, respectively. The data represents results of MTT assay expressed as the percentage of the cell viability in comparison to their control sample (cells incubated in serum-free DMEM without tested peptides), additional positive control corresponds to the cells incubated in the presence of 10% FCS. All experiments were performed independently in triplicate. *P < 0.05, **P < 0.01, ***P < 0.001 vs. control.
Mentions: Pro-proliferative properties of the tested compounds was analyzed towards immortal human keratinocyte cell line (HaCaT) and fibroblasts obtained from healthy human skin biopsies (Fig 1A and 1B). [17,18].

Bottom Line: Herein, we present the initial results of our studies aimed at the design of bifunctional peptide-based compounds.The chemical approach, that was utilized in this work, was based on the conjugation of antimicrobial peptides with the peptides, that have potential pro-proliferative and/or cytoprotective activity towards human keratinocytes and fibroblasts, in order to obtain antimicrobials with reduced cytotoxicity or compounds that maintain both activities, i.e. inhibit bacterial or fungi growth and activate cell proliferation/migration in in vitro tests.As a result, we obtained a group of peptide conjugates that effectively inhibited the growth of selected bacterial and fungi strains and were able to stimulate proliferation and migration of keratinocytes and fibroblasts under their effective microbicidal concentrations.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Chemistry, University of Gdansk, Gdansk, Poland.

ABSTRACT
Skin represents the largest organ of the human body and plays a crucial role in its protection from the negative impact of the outside environment, maintains its homeostasis, enables sensory interaction and thermoregulation. The traumatized skin tissue undergoes several phenotype switches due to progressive reoxygenation and release of cytokine and growth factors, that activate mechanisms of reparative processes. However, in case of wounds colonized with pathogenic microflora natural regenerative mechanisms become substantially impaired, that could lead to chronic inflammatory states with non-healing skin lesions. Herein, we present the initial results of our studies aimed at the design of bifunctional peptide-based compounds. The chemical approach, that was utilized in this work, was based on the conjugation of antimicrobial peptides with the peptides, that have potential pro-proliferative and/or cytoprotective activity towards human keratinocytes and fibroblasts, in order to obtain antimicrobials with reduced cytotoxicity or compounds that maintain both activities, i.e. inhibit bacterial or fungi growth and activate cell proliferation/migration in in vitro tests. As a result, we obtained a group of peptide conjugates that effectively inhibited the growth of selected bacterial and fungi strains and were able to stimulate proliferation and migration of keratinocytes and fibroblasts under their effective microbicidal concentrations.

No MeSH data available.


Related in: MedlinePlus