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. 2019 Oct 15;24(20):3698.
doi: 10.3390/molecules24203698.

The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity

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Free PMC article

The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity

Urszula Tałałaj et al. Molecules. .
Free PMC article

Abstract

KTTKS is a matrikine that originates from the proteolytic hydrolysis of collagen. This peptide stimulates ECM production and types I and III collagen expression in vitro. A more stable form of KTTKS is pal-KTTKS, known as Matrixyl® or palmitoyl pentapeptide-3. A series of novel pentapeptides, analogues of KTTKS with the general formula X-KTTKS-OH(NH2), where X = acetyl, lipoyl, palmitoyl residues, was designed and synthesized. Their effect on amidolytic activity of urokinase, thrombin, trypsin, plasmin, t-PA, and kallikrein were tested. Cytotoxic tests on fibroblasts, as well as collagen and DNA biosynthesis tests for selected peptides, were also carried out. The test results showed that the most active plasmin inhibitors were palmitoyl peptides, whether in acid or amide form. No biological effects of lysine modification to arginine in the synthesized peptides were found. None of the synthesized peptides was not cytotoxic on fibroblasts, and three of them showed cell growth. These three compounds showed no concentration-activity relationship in the collagen and DNA biosynthesis assays.

Keywords: KTTKS; collagen biosynthesis; cosmetic peptides; cytotoxity; palmitoyl pentapeptide; plasmin inhibitors.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Inhibition of plasmin, urokinase, and thrombin by 1–32 peptides presented as -logIC50.
Figure 2
Figure 2
Viability of fibroblast cells treated for 24 h with different concentrations of the tested peptides 1–32 (Table 3).
Figure 3
Figure 3
Influence of the synthesized peptides 13, 14 and 26 on DNA biosynthesis.
Figure 4
Figure 4
Influence of the synthetized peptides 13, 14 and 26 on collagen biosynthesis.
Figure 5
Figure 5
Influence of peptides in the form of C-terminal acids and amides on plasmin, urokinase and thrombin activity. Inhibition values in the form of -logIC50 from Table 3.
Figure 6
Figure 6
Influence of the introduction of N-terminal acetyl group in the synthetized peptides on plasmin, urokinase and thrombin inhibition. Inhibition values in the form of -logIC50 from Table 3.
Figure 7
Figure 7
Influence of the introduction of N-terminal lipoic group in the synthetized peptides on plasmin, urokinase, thrombin inhibition. Inhibition values in the form of -logIC50 from Table 2.
Figure 8
Figure 8
Influence of the introduction of N-terminal palmitic group in the synthetized peptides on plasmin, urokinase and thrombin inhibition. Inhibition values in the form of -logIC50 from Table 2.
Figure 9
Figure 9
Influence of the synthetized peptides on plasmin, urokinase and thrombin activity with substitution of amino acids in sequences taken into account. Values in the form of -logIC50.

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