Synthesis and biological evaluation of dimeric peptide derivatives as proliferation‐stimulating agents in human follicle dermal papilla cells

Abstract

Tripeptides containing lysine such as Arg‐His‐Lys (AHK) and Gly‐His‐Lys (GHK) are known to modulate biological regeneration. Here, we synthesized and evaluated the biological effects of dimeric peptide derivatives on the proliferation of human follicle dermal papilla cells (HFDPCs) in an in vitro model. Treatment of dimeric peptide derivatives stimulated the proliferation of HFDPCs more when compared to the group treated with AHK. Dimeric peptide derivatives also stimulated the phosphorylation of mitogen‐activated protein kinases extracellular signal‐regulated kinase (ERK1/2). In particular, peptide No. 20 Arg‐Trp‐Lys (AWK') was found to promote the phosphorylation of ERK1/2 most strongly. In addition, peptide No. 20 (AWK') activated mRNA expression of hair regeneration‐related genes such as VEGF, FGF‐2, and FGF‐7. Our results suggest that dimeric peptide derivatives exert a stimulating effect on HFDPC proliferation through activation of ERK1/2 signaling and without significant cytotoxicity. These results provide important data for the development of peptide‐based hair‐regenerative agents and treatment of alopecia.

Synthesis and biological evaluation of cilengitide derivatives on TGF‐β1‐induced epithelial‐to‐mesenchymal transition in human non‐small cell lung cancer cells

“…The detailed experimental procedure followed the materials and methods of the previous study. [10][11][12]25] The band intensities of proteins visualized using Sup-erSignal™ West Femto Maximum Sensitivity Substrate (Thermo Fisher Scientific). The detected bands were quantified using ImageJ software, and the relative ratios between each sample and the loading control are presented in the figures.…”

Combination effect of cilengitide derivatives with gefitinib onTGF‐β1‐induced epithelial‐to‐mesenchymal transition in human non‐small cell lung cancer cells

“…All cell lysates were prepared using Nuclear and Cytoplasmic Extraction Reagent (Thermo Fisher Scientific). 10,11,34 Isolated lysates were separated by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and transferred to nitrocellulose membranes. All antibodies were used at a dilution of 1:1000.…”

Synthesis and biological investigation of protein phosphatase 2A‐activating compounds with dimeric tail as non‐small cell lung cancer cell death agents

“…In this report, derivatives with a dimeric tail structure, such as Compound 4a (Figure 1), significantly improved the stability and anticancer activity of PF‐543. These dimeric molecular structures have often been used in physiologically active substances 15,16 . Based on these results, we tried to investigate whether the biological activity of FTY720 could be improved by introducing a dimeric aliphatic tail into the backbone of FTY720 (Supporting Information S1).…”

“…These dimeric molecular structures have often been used in physiologically active substances. 15,16 Based on these results, we tried to investigate whether the biological activity of FTY720 could be improved by introducing a dimeric aliphatic tail into the backbone of FTY720 (Supporting Information S1).…”