Copper(II), Nickel(II) and Zinc(II) Complexes of Peptide Fragments of Tau Protein
Abstract
:1. Introduction
2. Results and Discussion
2.1. The Acid–Base Properties of the Peptides
2.2. Copper(II) Complexes of the Peptides
2.3. Copper-Catalyzed Oxidation of Peptides
2.4. Zinc(II) Complexes of Peptides
2.5. Nickel(II) Complexes of Peptides
- The presence of proline significantly alters the complex formation processes of nickel(II) ions. This is especially true for tau(91–97), where amide coordination is not possible toward the N-terminus. In principle, it can occur on the C-terminal side of histidine, but the thermodynamic stability of the seven-membered chelate is much lower, and the corresponding species can be formed only under strongly alkaline conditions without any biological relevance. Thus, only the species [NiL] can be detected in the nickel(II)-tau(91–97) system. Its low stability constants, however, cannot prevent the hydrolysis of nickel(II) ions slightly above physiological pH.
- In the nickel(II)-tau(404–409) system, the deprotonation and coordination of one amide group is possible, the (Nim,N−) coordination mode, but the nickel(II) ion has two free coordination sites in this complex, resulting in hydrolytic reactions caused by increasing pH.
- Complex formation processes in the nickel(II)-tau(385–390) and tau(26–33)(mutant) systems are quite similar to each other. The deprotonation of three amide groups is possible, resulting in the (Nim,3N−) coordination mode above pH 8. The visible absorption (see Figure A5 in Appendix A) and circular dichroism spectroscopic measurements (see Figure A6 in Appendix A) strongly support the suggested coordination modes. It is also important to note that the pH-dependent changes in CD absorption are similar for the nickel(II) complexes of tau(385–390) and tau(26–33) mutant but differ from those of peptides missing the –TXH- sequence (Figure A7). A detailed investigation of the CD spectra of (Nim,3N−)-coordinated Ni(II) complexes of peptides containing the -TXH- or -SXH- sequence [33,34] also shows that an intense negative extreme appears at around 500 nm, together with a positive peak between 430 and 451 nm. In some cases, an additional positive extremum can be observed at around 560 nm. The CD spectral pattern of the [NiH−3L] complex of tau(385–390) corresponds to the latter case [33].
3. Materials and Methods
3.1. Materials
3.2. Potentiometric Measurements
3.3. Spectroscopic Measurements (UV-Vis and CD Spectroscopy)
3.4. Oxidation of Tau Fragment
3.5. Isolation of Oxidized Products
3.6. HPLC-MS Measurements
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A. Copper(II), Nickel(II) and Zinc(II) Complexes of Peptide Fragments of tau Protein
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Species | tau(91–97) (Ac-AQPHTEI-NH2) | tau(385–390) (Ac-KTDHGA-NH2) | tau(404–409) (Ac-SPRHLS-NH2) | tau(9–16) (Ac-EVMEDHAG-NH2) [21] | tau(26–33) (Ac-QGGYTMHQ-NH2) [21] |
---|---|---|---|---|---|
HL | 6.60(1) | 10.34(1) | 6.24(1) | 6.70 | 9.48 |
H2L | 10.72(1) | 16.85(1) | – | 11.38 | 15.50 |
H3L | – | 20.41(1) | – | 15.52 | – |
H4L | – | – | – | 18.93 | – |
pK(Im) | 6.60 | 6.51 | 6.24 | 6.70 | 6.02 |
pK(Asp) | – | 3.56 | – | 3.41 | – |
pK(Glu)1 | 4.12 | – | – | 4.14 | – |
pK(Glu)2 | – | – | – | 4.68 | – |
pK(Lys) | – | 10.34 | – | – | – |
pK(Tyr) | – | – | – | – | 9.48 |
Species | tau(91–97) (Ac-AQPHTEI-NH2) | tau(385–390) (Ac-KTDHGA-NH2) | tau(404–409) (Ac-SPRHLS-NH2) | tau(9–16) (Ac-EVMEDHAG-NH2) [21] | tau(26–33) (Ac-QGGYTMHQ-NH2) [21] |
---|---|---|---|---|---|
[CuHL] | – | 14.43(4) | – | 9.66 | 13.26 |
[CuL] | 5.02(4) | – | 3.33(12) | 5.04 | – |
[CuH−1L] | – | 3.41(2) | – | – | 3.23 |
[CuH−2L] | −10.73(7) | −5.24(4) | −8.22(4) | −8.09 | −5.60 |
[CuH−3L] | – | −15.28(4) | −18.49(6) | −16.61 | −15.47 |
[CuH−4L] | −30.20(7) | – | −29.18(4) | – | – |
logK(Cu(II) + Nim) | 5.02 | 4.09 | 3.33 | 5.04 | 3.78 |
pK1,2amide (av.) | 7.875 | 5.51 | 5.775 | 6.57 | 5.01 |
pK3amide | 9.735 (av.) | 8.65 | 10.27 | 8.52 | 8.83 |
pK4amide | – | 10.69 | – | – |
Coordination Mode | tau(91–97) (Ac-AQPHTEI-NH2) | tau(385–390) (Ac-KTDHGA-NH2) | tau(404–409) (Ac-SPRHLS-NH2) | tau(9–16) (Ac-EVMEDHAG-NH2) [21] | tau(26–33) (Ac-QGGYTMHQ-NH2) [21] |
---|---|---|---|---|---|
Nim (+COO−) | 714(45) | 750(15) * | 790(15) * | 747(38) | – |
N−,N−,Nim | 622(98) | 588(77) | 602(84) | 616(74) | 590(75) |
N−,N−,N−,Nim | – | 561(81) | 577(85) | 530(144) | 551(87) |
N−,N−,N−,N− | 532(115) | – | 531(174) | – | – |
Species | tau(91–97) (Ac-AQPHTEI-NH2) | tau(385–390) (Ac-KTDHGA-NH2) | tau(404–409) (Ac-SPRHLS-NH2) | tau(9–16) (Ac-EVMEDHAG-NH2) [23] | tau(26–33)m (Ac-KGGYTMHK-NH2) [23] |
---|---|---|---|---|---|
[NiH3L] | – | – | – | – | 32.92 |
[NiH2L] | – | – | – | – | 25.29 |
[NiHL] | – | 13.03(4) | – | – | – |
[NiL] | 4.20(6) | 5.01(3) | 1.98(9) | 3.47 | 9.44 |
[NiH–1L] | −2.96(7) | – | −6.31(8) | −4.95 | 0.19 |
[NiH–2L] | – | −11.78(2) | – | – | –10.08 |
[NiH–3L] | – | −21.78(2) | – | −22.56 | −20.52 |
logK(Ni(II) + Nim) | 4.20 | 2.69 | 1.98 | 3.47 | 2.70 |
pK1amide | – | 8.09 | 8.29 | 8.42 | 7.67 |
pK2,3amide (av) | – | 8.40 | – | 8.805 | 7.92 |
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Kastal, Z.; Balabán, A.; Vida, S.; Kállay, C.; Nagy, L.; Várnagy, K.; Sóvágó, I. Copper(II), Nickel(II) and Zinc(II) Complexes of Peptide Fragments of Tau Protein. Molecules 2024, 29, 2171. https://doi.org/10.3390/molecules29102171
Kastal Z, Balabán A, Vida S, Kállay C, Nagy L, Várnagy K, Sóvágó I. Copper(II), Nickel(II) and Zinc(II) Complexes of Peptide Fragments of Tau Protein. Molecules. 2024; 29(10):2171. https://doi.org/10.3390/molecules29102171
Chicago/Turabian StyleKastal, Zsuzsa, Adrienn Balabán, Szilvia Vida, Csilla Kállay, Lajos Nagy, Katalin Várnagy, and Imre Sóvágó. 2024. "Copper(II), Nickel(II) and Zinc(II) Complexes of Peptide Fragments of Tau Protein" Molecules 29, no. 10: 2171. https://doi.org/10.3390/molecules29102171
APA StyleKastal, Z., Balabán, A., Vida, S., Kállay, C., Nagy, L., Várnagy, K., & Sóvágó, I. (2024). Copper(II), Nickel(II) and Zinc(II) Complexes of Peptide Fragments of Tau Protein. Molecules, 29(10), 2171. https://doi.org/10.3390/molecules29102171