Covalent Modification of Human Serum Albumin by the Natural Sesquiterpene Lactone Parthenolide
Abstract
:1. Introduction
2. Results and Discussion
2.1. LC/MS-Analysis of Untreated HSA Digest
Tryptic Fragment No. | Theoretical Molecular Mass of [M+H]+ | Molecular Mass of [M+H]+ after Deconvolution | Deviation (mDa/ppm) | Charge States (n) of Detected Ions [M+nH]n+ | Retention Time (min) | Compound No. (Figure 2b) |
---|---|---|---|---|---|---|
1 | 470.2358 | 470.2340 | 1.8/3.8 | 1 | 0.99 | 1 |
2 | 698.3580 | 698.3579 | 0.1/1.0 | 1, 2 | 1.13 | 2 |
3 | 294.1812 | n.d. | ||||
4 | 951.4418 | 951.4377 | 4.1/4.3 | 1, 2 | 3.72 | 17 |
5 | 2433.2635 | n.d. | ||||
5-SS-5 | 4863.5037 | 4863.5344 | 30.7/6.3 | 4, 5, 6, 7 | 17.87 | 156 |
5-SS-Cys | 2552.2676 | 2552.2778 | 10.2/4.0 | 3, 4, 5 | 15.38 | 143 |
5-SS-hCys | 2566.2832 | 2566.3146 | 31/12.1 | 3, 4, 5 | 9.00 | 75 |
6 | 1149.6150 | 1149.6221 | 7.1/6.2 | 1,2 | 7.10 | 51 |
7 | 1382.5195 | 1382.5358 | 16.3/11.8 | 1, 2 | 1.19 | 3 |
8 | 1017.5364 | 1017.5353 | 1.1/1.1 | 1, 2, 3 | 6.98 | 50 |
9 + 10 + 11 + 12 | 3848.7117 | 3848.7399 | 28.2/7.3 | 5, 6 | 6.32 | 42 |
13 | 940.4483 | 940.4493 | 1.0/1.1 | 1,2 | 1.78 | 9 |
14 + 18 + 19 | 4560.1368 | 4560.1741 | 37.3/8.2 | 4, 5, 6, 7, 8 | 9.53 | 82 |
15 | 927.4934 | 927.4921 | 1.3/1.4 | 1, 2 | 6.49 | 44 |
16 | 1742.8941 | 1742.8983 | 4.2/2.4 | 2, 3 | 3.43 | 135 |
17 | 310.1761 | n.d. | ||||
20 | 645.3566 | 645.3621 | 5.5/8.5 | 1, 2 | 1.96 | 11 |
21 | 448.2038 | n.d. | ||||
22 | 463.2511 | 463.2496 | 1.5/3.2 | 1 | 0.99 | 1 |
23 | 303.1775 | n.d. | ||||
24 | 260.1969 | n.d. | ||||
25 + 33 | 2560.0676 | 2560.0647 | 2.9/1,1 | 4, 5 | 5.64 | 33 |
26 | 508.2514 | 508.2525 | 1.1/2.2 | 1 | 1.25 | 4 |
27 | 365.2183 | 365.2185 | 0.2/0.5 | 1 | 1.19 | 3 |
28 | 673.3780 | 673.3788 | 0.8/1.2 | 1, 2 | 3.43 | 16 |
29 | 503.2936 | 503.2932 | 0.4/0.8 | 1 | 1.13 | 2 |
30 | 391.2340 | 391.2326 | 1.4/3.6 | 1 | 1.32 | 5 |
31 | 880.4411 | 880.4411 | 0/0 | 1, 2 | 2.46 | 14 |
32 | 789.4716 | 789.4691 | 2.5/3.2 | 1, 2 | 3.98 | 18 |
34 | 517.2980 | 517.2995 | 1.5/2.9 | 1 | 1.19 | 3 |
35 + 36 + 37 + 38 | 5730.6464 | 5,730.6533 | 6.9/1.2 | 4, 5, 6, 7, 8, 9 | 11.14 | 104 |
39 | 464.2173 | n.d. | ||||
40 | 695.3359 | 695.3439 | 8.0/11.5 | 1 | 1.19 | 3 |
41 | 1623.7876 | 1623.7938 | 6.2/3.8 | 2, 3 | 15.36 | 142 |
42 | 1311.7419 | 1311.7362 | 5.7/4.3 | 1, 2, 3 | 12.39 | 118 |
43 | 331.2340 | 331.2354 | 1.4/4.2 | 1 | 1.19 | 3 |
44 | 984.4884 | 984.4889 | 0.5/0.5 | 1, 2 | 2.07 | 12 |
45 | 1381.5334 | n.d. | ||||
46 | 2045.0954 | 2,045.1124 | 17.0/8.3 | 2, 3, 4 | 11.56 | 110 |
47 | 1600.7312 | n.d. | ||||
48 | 960.5630 | 960.5584 | 4.6/4.8 | 1, 2 | 7.54 | 56 |
49 | 411.2238 | n.d. | ||||
50 | 1511.8428 | 1511.8521 | 9.3/6.2 | 2, 3 | 8.21 | 66 |
51 | 431.2613 | 431.2608 | 0.5/1.2 | 1 | 1.19 | 3 |
52 | 390.2350 | 390.2300 | 5.0/17.2 | 1 | 0.99 | 1 |
53 | 353.1312 | n.d. | ||||
54 | 581.3052 | n.d. | ||||
55 | 2404.1709 | n.d. | ||||
56 | 674.3468 | 674.3529 | 6.1/9.0 | 1 | 1.19 | 3 |
57 | 347.2289 | n.d. | ||||
58 | 1024.4550 | n.d. | ||||
59 | 1853.9102 | n.d. | ||||
60 + 68 + 69 + 70 + 71 | 3563.5102 | 3,563.6537 | 143/40 | 4, 5 | 12.21 | 116 |
61 | 304.1615 | n.d. | ||||
62 | 388.2554 | 388.2550 | 0.4/1.0 | 1 | 1.19 | 3 |
63 | 1000.6037 | 1000.6029 | 0.8/0.8 | 1, 2 | 8.47 | 69 |
64 | 509.3194 | 509.3184 | 1.0/2.0 | 1 | 0.99 | 1 |
65 | 319.1976 | n.d. | ||||
66 | 517.2980 | 517.2995 | 1.5/2.9 | 1 | 1.19 | 3 |
67 | 1342.6348 | 1342.6417 | 6.9/5.1 | 2, 3 | 11.26 | 105 |
68 | 1013.5990 | 1013.6084 | 9.4/9.3 | 1, 2 | 9.06 | 76 |
2.2. Covalent Modification of C34 by Parthenolide
2.3. Time Course of the Reaction between Parthenolide and HSA
3. Experimental Section
3.1. Investigated Compounds
3.2. Sample Preparation
3.2.1. Preparation of Parthenolide-HSA Conjugate
3.2.2. Tryptic Digestion
3.3. High-Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry
3.4. Data Analysis
3.5. Time Course of the Reaction of HSA with PRT and DHP
4. Conclusions
Author Contributions
Conflicts of Interest
References
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Plöger, M.; Sendker, J.; Langer, K.; Schmidt, T.J. Covalent Modification of Human Serum Albumin by the Natural Sesquiterpene Lactone Parthenolide. Molecules 2015, 20, 6211-6223. https://doi.org/10.3390/molecules20046211
Plöger M, Sendker J, Langer K, Schmidt TJ. Covalent Modification of Human Serum Albumin by the Natural Sesquiterpene Lactone Parthenolide. Molecules. 2015; 20(4):6211-6223. https://doi.org/10.3390/molecules20046211
Chicago/Turabian StylePlöger, Michael, Jandirk Sendker, Klaus Langer, and Thomas J. Schmidt. 2015. "Covalent Modification of Human Serum Albumin by the Natural Sesquiterpene Lactone Parthenolide" Molecules 20, no. 4: 6211-6223. https://doi.org/10.3390/molecules20046211