Nerve Growth Factor Peptides Bind Copper(II) with High Affinity: A Thermodynamic Approach to Unveil Overlooked Neurotrophin Roles
Abstract
:1. Introduction
2. Results
2.1. Protonation Constants
2.2. Speciation and Characterization of Copper-Peptide Complexes
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Chemicals
5.2. Potentiometric Titrations
5.3. UV–Vis and CD Measurements
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Species | NGF(1-14) b | rNGF(14-1) | sNGF(1-14) | dNGF(1-15) |
---|---|---|---|---|
LH | 7.56 | 7.82 (2) | 7.85 (3) | 7.65 (5) |
LH2 | 14.13 | 14.51 (2) | 14.65 (3) | 15.35 (2) |
LH3 | 20.14 | 20.60 (2) | 20.87 (3) | - |
LH4 | 24.44 | 24.88 (2) | 25.11 (4) | 28.77 (6) |
LH5 | - | 35.12 (4) | ||
LH6 | - | 41.31 (4) | ||
LH7 | - | 46.62 (4) | ||
LH8 | - | 50.75 (4) | ||
pK COO- | 4.13 | 4.28 | 4.23 | 4.13 |
pK COO- | - | - | - | 5.28 |
pK His | 6.01 | 6.09 | 6.22 | 6.21 |
pK His | 6.57 | 6.69 | 6.81 | 6.35 |
pK His (×2) | - | - | - | (6.71 × 2) |
pK NH2 | 7.56 | 7.82 | 7.85 | 7.65 |
pK NH2 | - | 7.70 |
Species (pqr) b | logβpqr NGF(1-14)c | logβpqr rNGF(14-1) | logβpqr sNGF(1-14) | logβpqr dNGF(1-15) |
---|---|---|---|---|
CuLH5 | - | - | - | 41.18 (3) |
CuLH3 | - | - | - | 31.56 (2) |
CuLH2 | - | - | - | 25.91 (5) |
CuLH | 14.09 | 14.15 (1) | 13.97 (4) | 17.79 (5) |
CuL | 8.72 | 8.77 (1) | 8.32 (5) | 8.21 (4) |
CuLH-1 | 3.27 | 2.33 (2) | −2.74 (3) | - |
CuLH-2 | −4.02 | −6.15 (4) | −5.58 (8) | - |
CuLH-3 | −13.34 | −14.67 (2) | −13.27 (4) | - |
pK (n/m) | ||||
pK (5/3) | - | - | - | 4.81 × 2 |
pK (3/2) | - | - | - | 5.65 |
pK (2/1) | - | - | - | 8.12 |
pK (1/0) | 5.37 | 5.38 | 5.65 | 9.57 |
pK (0/−1) | 5.45 | 6.43 | 5.57 | - |
pK (−1/−2) | 7.29 | 8.48 | 8.33 | - |
pK (−2/−3) | 9.30 | 8.52 | 7.69 | - |
Peptide | pH | UV-vis λ (nm) (ε (M−1 cm−1)) | CD λ (nm) (Δε (M−1 cm−1) |
---|---|---|---|
rNGF(14-1) | 5 | 640 (64) | 280 (−0.30); 316 (+0.20); 670 (−0.27) |
6 | 625 (144) | 280 (−0.40); 323 (+0.33); 671 (−0.44) | |
7.4 | 609 (178) | 280 (−0.30); 314 (−0.22); 352 (+0.07); 508 (+0.31); 625 (−0.60) | |
9 | 532 (194) | 280 (−1.30); 484 (+0.46); 589 (−0.79) | |
10 | 522 (232) | 280 (−1.80); 483 (+0.54); 577 (−1.00) | |
sNGF(1-14) | 5 | 670 (40) | 289 (−0.20); 328 (+0.12); 647 (−0.04) |
6 | 617 (94) | 287 (−1.34); 328 (+0.68); 617 (−0.59) | |
7.4 | 603 (102) | 288 (−1.38); 329 (+0.82); 603 (−0.72) | |
9-10 | 522 (141) | 306 (+1.47); 544 (−1.13) | |
dNGF(1-15) | 5 | 635 (50) | 280 (−0.34); 321 (+0.19); 669 (−0.24) |
6 | 612 (70) | 280 (−0.40); 323 (+0.33); 671 (−0.44) | |
7.4 | 569 (94) | 280 (−1.80); 324 (+0.92); 504 (+0.08); 611 (−0.30) | |
8 | 561 (104) | 280 (−2.04); 323 (+0.98); 496 (+0.11); 586 (−0.34) | |
9 | 554 (119) | 280 (−2.15); 324 (+0.98); 496 (+0.08); 587 (−0.38) | |
10 | 530 (138) | 280 (−2.14); 324 (+0.71); 563 (−0.46) |
Peptide | pH | |
---|---|---|
NGF(1-14) | 7.4 | 2.5 × 10−11 |
dNGF(1-15) | 7.4 | 4.2 × 10−11 |
rNGF(14-1) | 7.4 | 6.5 × 10−10 |
sNGF(1-14) | 7.4 | 2.7 × 10−10 |
Aβ1-16-PEG a | 7.4 | 1.1 × 10−10 |
hCtr1-14 b | 7.4 | 1.0 × 10−13 |
NGF(1-14) | 5.5 | 4.0 × 10−6 |
dNGF(1-15) | 5.5 | 1.9 × 10−7 |
rNGF(14-1) | 5.5 | 1.4 × 10−5 |
sNGF(1-14) | 5.5 | 3.8 × 10−5 |
Aβ1-16-PEG | 5.5 | 2.5 × 10−7 |
hCtr1-14 | 5.5 | 7.4 × 10−8 |
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Magrì, A.; La Mendola, D.; Rizzarelli, E. Nerve Growth Factor Peptides Bind Copper(II) with High Affinity: A Thermodynamic Approach to Unveil Overlooked Neurotrophin Roles. Int. J. Mol. Sci. 2021, 22, 5085. https://doi.org/10.3390/ijms22105085
Magrì A, La Mendola D, Rizzarelli E. Nerve Growth Factor Peptides Bind Copper(II) with High Affinity: A Thermodynamic Approach to Unveil Overlooked Neurotrophin Roles. International Journal of Molecular Sciences. 2021; 22(10):5085. https://doi.org/10.3390/ijms22105085
Chicago/Turabian StyleMagrì, Antonio, Diego La Mendola, and Enrico Rizzarelli. 2021. "Nerve Growth Factor Peptides Bind Copper(II) with High Affinity: A Thermodynamic Approach to Unveil Overlooked Neurotrophin Roles" International Journal of Molecular Sciences 22, no. 10: 5085. https://doi.org/10.3390/ijms22105085