The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity
Abstract
:1. Introduction
2. Results
2.1. Peptide Synthesis
2.2. Enzymatic Investigations
2.3. Viability of Fibroblast Cells
2.4. DNA and Collagen Biosynthesis
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Peptide Synthesis
4.3. Enzymatic Investigations
- Tris buffer—0.6 mL (pH 8.8), enzyme: urokinase (50 units/mL), synthetic substrate: pyro-Glu-Gly-Arg-pNA·HCl (0.1 mL, 3 mM);
- Tris buffer—0.5 mL (pH 8.4), enzyme: thrombin (1 units/mL), synthetic substrate: H-D-Phe-Pip-Arg-pNA (0.2 mL, 0.75 mM);
- Tris buffer—0.5 mL (pH 7.4), enzyme: plasmin (0.4 units/mL), synthetic substrate: H-D-Val-Leu-Lys-pNA (0.2 mL, 3 mM);
- Borate buffer—0.5 mL (pH 7.5), enzyme: trypsin (0.4 units/mL), synthetic substrate: Bzl-L-Arg-pNA·HCl (0.2 mL, 8 mM);
- Tris buffer—0.6 mL (pH 9.0), enzyme: kallikrein (3 units/mL), synthetic substrate: H-D-Val-Leu-Arg-pNA·2HCl (0.1 mL, 75 mM);
- Tris buffer—0.6 mL (pH 8.4), enzyme: t-PA (167 mg/mL), synthetic substrate: H-D-Ile-Pro-Arg-pNA (0.1 mL, 10 mM)
- Tris buffer—0.6 mL (pH 9.0), enzyme: chymotrypsin (0.4 units/mL), synthetic substrate: Suc-Phe-pNA (0.2 mL, 8 mM)
4.4. Viability of Fibroblast Cells
4.4.1. Cell Culture
4.4.2. Cell Viability Assay
4.4.3. DNA Biosynthesis
4.4.4. Collagen Biosynthesis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
No | Peptide | IC50 [mM] | ||
---|---|---|---|---|
Plasmin | Urokinase | Thrombin | ||
1 | KTTKSOH | 0.28 ± 0.014 | 0.019 ± 0.00094 | 7.81 ± 0.39 |
2 | AcKTTKSOH | 2.78 ± 0.14 | 3.88 ± 0.19 | 2.20 ± 0.11 |
3 | LipKTTKSOH | 0.47 ± 0.023 | 0.024 ± 0.0012 | 12.83 ± 0.64 |
4 | PalKTTKSOH | 0.00071 ± 0.000035 | 0.00086 ± 0.000043 | 0.0018 ± 0.00009 |
5 | KTTKSNH2 | 0.53 ± 0.026 | 9.15 ± 0.46 | 7.04 ± 0.35 |
6 | AcKTTKSNH2 | 2.92 ± 0.15 | 61.76 ± 3.09 | 3.25 ± 0.16 |
7 | LipKTTKSNH2 | 0.58 ± 0.029 | 15.07 ± 0.75 | 11.70 ± 0.58 |
8 | PalKTTKSNH2 | 0.00021 ± 0.000010 | 3.12 ± 0.16 | 0.046 ± 0.0023 |
9 | KTTRSOH | 0.63 ± 0.031 | 0.011 ± 0.00054 | 4.01 ± 0.20 |
10 | AcKTTRSOH | 2.24 ± 0.11 | 4.82 ± 0.041 | 2.89 ± 0.14 |
11 | LipKTTRSOH | 0.24 ± 0.012 | 0.019 ± 0.00093 | 10.94 ± 0.54 |
12 | PalKTTRSOH | 0.00078 ± 0.000039 | 0.00080 ± 0.00004 | 0.012 ± 0.00058 |
13 | KTTRSNH2 | 0.72 ± 0.036 | 17.62 ± 0.88 | 4.65 ± 0.23265 |
14 | AcKTTRSNH2 | 5.34 ± 0.27 | 5.56 ± 0.28 | 2.95 ± 0.15 |
15 | LipKTTRSNH2 | 0.69 ± 0.035 | 3.47 ± 0.17 | 4.11 ± 0.21 |
16 | PalKTTRSNH2 | 0.00086 ± 0.000043 | 2.37 ± 0.12 | 0.0018 ± 0.00009 |
17 | RTTRSOH | 0.28 ± 0.014 | 0.015 ± 0.00076 | 3.89 ± 0.19 |
18 | AcRTTRSOH | 8.81 ± 0.44 | 3.24 ± 0.16 | 3.12 ± 0.16 |
19 | LipRTTRSOH | 1.014 ± 0.051 | 0.022 ± 0.0011 | 1.84 ± 0.092 |
20 | PalRTTRSOH | 0.00055 ± 0.000027 | 0.00049 ± 0.000024 | 0.03004 ± 0.0015 |
21 | RTTRSNH2 | 0.44 ± 0.022 | 11.97 ± 0.59 | 2.93 ± 0.14 |
22 | AcRTTRSNH2 | 9.08 ± 0.45 | 24.96 ± 1.25 | 1.47 ± 0.074 |
23 | LipRTTRSNH2 | 1.89 ± 0.094 | 4.67 ± 0.23 | 2.36 ± 0.12 |
24 | PalRTTRSNH2 | 0.00042 ± 0.000021 | 0.26 ± 0.013 | 0.041 ± 0.0020 |
25 | RTTKSOH | 0.54 ± 0.027 | 0.0106 ± 0.00053 | 2.51 ± 0.13 |
26 | AcRTTKSOH | 5.45 ± 0.27 | 2.36 ± 0.12 | 0.81 ± 0.041 |
27 | LipRTTKSOH | 2.12 ± 0.11 | 0.097 ± 0.0049 | 4.23 ± 0.12 |
28 | PalRTTKSOH | 0.00067 ± 0.000033 | 0.00048 ± 0.000024 | 0.0021 ± 0.00011 |
29 | RTTKSNH2 | 0.30 ± 0.015 | 7.95 ± 0.40 | 2.43 ± 0.12 |
30 | AcRTTKSNH2 | 5.00 ± 0.25 | 12.07 ± 0.60 | 1.59 ± 0.080 |
31 | LipRTTKSNH2 | 3.23 ± 0.16 | 4.57 ± 0.23 | 5.59 ± 0.28 |
32 | PalRTTKSNH2 | 0.00045 ± 0.000023 | 0.49 ± 0.024 | 0.0306 ± 0.0015 |
No | Compound | -logIC50 | ||
---|---|---|---|---|
Plasmin | Urokinase | Thrombin | ||
1 | KTTKSOH | 3.55 ± 0.18 | 4.72 ± 0.24 | 2.11 ± 0.11 |
2 | AcKTTKSOH | 2.56 ± 0.13 | 2.41 ± 0.12 | 2.66 ± 0.13 |
3 | LipKTTKSOH | 3.33 ± 0.17 | 4.63 ± 0.23 | 1.89 ± 0.09 |
4 | PalKTTKSOH | 6.15 ± 0.31 | 6.06 ± 0.30 | 5.75 ± 0.29 |
5 | KTTKSNH2 | 3.28 ± 0.16 | 2.04 ± 0.10 | 2.15 ± 0.11 |
6 | AcKTTKSNH2 | 2.53 ± 0.13 | 1.21 ± 0.06 | 2.49 ± 0.12 |
7 | LipKTTKSNH2 | 3.24 ± 0.16 | 1.82 ± 0.09 | 1.93 ± 0.10 |
8 | PalKTTKSNH2 | 6.67 ± 0.33 | 2.51 ± 0.13 | 4.34 ± 0.22 |
9 | KTTRSOH | 3.20 ± 0.16 | 4.96 ± 0.25 | 2.40 ± 0.12 |
10 | AcKTTRSOH | 2.65 ± 0.13 | 2.32 ± 0.12 | 2.54 ± 0.13 |
11 | LipKTTRSOH | 3.61 ± 0.18 | 4.73 ± 0.24 | 1.96 ± 0.10 |
12 | PalKTTRSOH | 6.11 ± 0.31 | 6.10 ± 0.30 | 4.93 ± 0.25 |
13 | KTTRSNH2 | 3.15 ± 0.16 | 1.75 ± 0.09 | 2.33 ± 0.12 |
14 | AcKTTRSNH2 | 2.27 ± 0.11 | 2.25 ± 0.11 | 2.53 ± 0.13 |
15 | LipKTTRSNH2 | 3.16 ± 0.16 | 2.46 ± 0.12 | 2.39 ± 0.12 |
16 | PalKTTRSNH2 | 6.07 ± 0.30 | 2.63 ± 0.13 | 5.75 ± 0.29 |
17 | RTTRSOH | 3.54 ± 0.18 | 4.82 ± 0.24 | 2.41 ± 0.12 |
18 | AcRTTRSOH | 2.05 ± 0.10 | 2.49 ± 0.12 | 2.51 ± 0.13 |
19 | LipRTTRSOH | 2.99 ± 0.15 | 4.66 ± 0.23 | 2.74 ± 0.14 |
20 | PalRTTRSOH | 6.26 ± 0.31 | 6.31 ± 0.32 | 4.52 ± 0.23 |
21 | RTTRSNH2 | 3.36 ± 0.17 | 1.92 ± 0.10 | 2.53 ± 0.13 |
22 | AcRTTRSNH2 | 2.04 ± 0.10 | 1.60 ± 0.08 | 2.83 ± 0.14 |
23 | LipRTTRSNH2 | 2.72 ± 0.14 | 2.33 ± 0.12 | 2.63 ± 0.13 |
24 | PalRTTRSNH2 | 6.38 ± 0.32 | 3.59 ± 0.18 | 4.39 ± 0.22 |
25 | RTTKSOH | 3.27 ± 0.16 | 4.97 ± 0.25 | 2.60 ± 0.13 |
26 | AcRTTKSOH | 2.26 ± 0.11 | 2.63 ± 0.13 | 3.09 ± 0.15 |
27 | LipRTTKSOH | 2.67 ± 0.13 | 4.01 ± 0.20 | 2.37 ± 0.12 |
28 | PalRTTKSOH | 6.18 ± 0.31 | 6.32 ± 0.32 | 5.67 ± 0.28 |
29 | RTTKSNH2 | 3.51 ± 0.18 | 2.10 ± 0.10 | 2.61 ± 0.13 |
30 | AcRTTKSNH2 | 2.30 ± 0.12 | 1.92 ± 0.10 | 2.80 ± 0.14 |
31 | LipRTTKSNH2 | 2.49 ± 0.12 | 2.34 ± 0.12 | 2.25 ± 0.11 |
32 | PalRTTKSNH2 | 6.34 ± 0.32 | 3.31 ± 0.17 | 4.51 ± 0.23 |
Synthesized Peptides | ||||||||||||||||
Concentration [µmol/L] | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 |
1 | 95 | 98 | 94 | 97 | 91 | 97 | 97 | 96 | 93 | 104 | 102 | 103 | 121 | 112 | 112 | 104 |
10 | 82 | 88 | 81 | 91 | 91 | 88 | 89 | 83 | 103 | 100 | 105 | 98 | 139 | 135 | 122 | 114 |
100 | 80 | 82 | 81 | 85 | 100 | 86 | 87 | 83 | 101 | 94 | 98 | 99 | 145 | 150 | 115 | 115 |
Synthesized Peptides | ||||||||||||||||
Concentration [µmol/L] | 17 | 18 | 19 | 20 | 21 | 22 | 23 | 24 | 25 | 26 | 27 | 28 | 29 | 30 | 31 | 32 |
1 | 89 | 88 | 79 | 90 | 84 | 102 | 89 | 94 | 97 | 112 | 105 | 104 | 101 | 95 | 107 | 104 |
10 | 99 | 103 | 81 | 90 | 94 | 99 | 79 | 104 | 87 | 137 | 91 | 103 | 111 | 105 | 112 | 113 |
100 | 115 | 107 | 90 | 103 | 103 | 101 | 88 | 97 | 109 | 150 | 80 | 106 | 110 | 101 | 117 | 118 |
Peptides | |||
---|---|---|---|
Concentration [µmol/L] | 13 | 14 | 26 |
10 | 84 | 114 | 126 |
50 | 86 | 96 | 112 |
100 | 74 | 127 | 128 |
Peptides | |||
---|---|---|---|
Concentration [µmol/L] | 13 | 14 | 26 |
10 | 10 | 105 | 166 |
50 | 155 | 171 | 77 |
100 | 49 | 157 | 108 |
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Tałałaj, U.; Uścinowicz, P.; Bruzgo, I.; Surażyński, A.; Zaręba, I.; Markowska, A. The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity. Molecules 2019, 24, 3698. https://doi.org/10.3390/molecules24203698
Tałałaj U, Uścinowicz P, Bruzgo I, Surażyński A, Zaręba I, Markowska A. The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity. Molecules. 2019; 24(20):3698. https://doi.org/10.3390/molecules24203698
Chicago/Turabian StyleTałałaj, Urszula, Paulina Uścinowicz, Irena Bruzgo, Arkadiusz Surażyński, Ilona Zaręba, and Agnieszka Markowska. 2019. "The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity" Molecules 24, no. 20: 3698. https://doi.org/10.3390/molecules24203698