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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

Stimulating effect of DAL-PEG-KSLW peptide on the migration of keratinocytes and fibroblasts after 24 hours of incubation.A—control probe for keratinocytes, B—migration of keratinocytes in the presence of the peptide (25 μg/mL), C—the control probe for fibroblasts, D- migration of fibroblasts in the presence of the peptide (25 μg/mL). HaCaT cells and fibroblasts were grown on the 6-well plates to confluence. Then cells were serum-starved for the next 12 hours. After that, the medium was changed and cells were stimulated with the tested peptides applied at concentration of 25 μg/mL. Incubation was continued for the next 24 hours, then cells were fixed, dyed with 0.05% of crystal violet and analyzed using Zeiss Observer D1 microscope.
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pone.0140377.g003: Stimulating effect of DAL-PEG-KSLW peptide on the migration of keratinocytes and fibroblasts after 24 hours of incubation.A—control probe for keratinocytes, B—migration of keratinocytes in the presence of the peptide (25 μg/mL), C—the control probe for fibroblasts, D- migration of fibroblasts in the presence of the peptide (25 μg/mL). HaCaT cells and fibroblasts were grown on the 6-well plates to confluence. Then cells were serum-starved for the next 12 hours. After that, the medium was changed and cells were stimulated with the tested peptides applied at concentration of 25 μg/mL. Incubation was continued for the next 24 hours, then cells were fixed, dyed with 0.05% of crystal violet and analyzed using Zeiss Observer D1 microscope.

Mentions: As illustrated in Fig 2 all of the tested peptides had a pro-migratory effect on the keratinocytes, with the best results obtained for KSLW, DAL-PEG-KSLW and CAR. Migration of the cells in this case was comparable to the effect induced by 10% FCS and more pronounced than in case of the control probe. It is worth of mentioning, that migration stimulated by the conjugate DAL-PEG-KSLW (Fig 3) was about 15% higher than that observed for the native peptides KSLW and DAL.


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)

Stimulating effect of DAL-PEG-KSLW peptide on the migration of keratinocytes and fibroblasts after 24 hours of incubation.A—control probe for keratinocytes, B—migration of keratinocytes in the presence of the peptide (25 μg/mL), C—the control probe for fibroblasts, D- migration of fibroblasts in the presence of the peptide (25 μg/mL). HaCaT cells and fibroblasts were grown on the 6-well plates to confluence. Then cells were serum-starved for the next 12 hours. After that, the medium was changed and cells were stimulated with the tested peptides applied at concentration of 25 μg/mL. Incubation was continued for the next 24 hours, then cells were fixed, dyed with 0.05% of crystal violet and analyzed using Zeiss Observer D1 microscope.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140377.g003: Stimulating effect of DAL-PEG-KSLW peptide on the migration of keratinocytes and fibroblasts after 24 hours of incubation.A—control probe for keratinocytes, B—migration of keratinocytes in the presence of the peptide (25 μg/mL), C—the control probe for fibroblasts, D- migration of fibroblasts in the presence of the peptide (25 μg/mL). HaCaT cells and fibroblasts were grown on the 6-well plates to confluence. Then cells were serum-starved for the next 12 hours. After that, the medium was changed and cells were stimulated with the tested peptides applied at concentration of 25 μg/mL. Incubation was continued for the next 24 hours, then cells were fixed, dyed with 0.05% of crystal violet and analyzed using Zeiss Observer D1 microscope.
Mentions: As illustrated in Fig 2 all of the tested peptides had a pro-migratory effect on the keratinocytes, with the best results obtained for KSLW, DAL-PEG-KSLW and CAR. Migration of the cells in this case was comparable to the effect induced by 10% FCS and more pronounced than in case of the control probe. It is worth of mentioning, that migration stimulated by the conjugate DAL-PEG-KSLW (Fig 3) was about 15% higher than that observed for the native peptides KSLW and DAL.

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