The Palladium(II) Complex of A<i>β</i><sub>4−16</sub> as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids
The A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>42</mn></mrow></msub></semantics></math></inline-formula> peptide is a major beta...
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/9200 |
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| author | Mariusz Mital Kosma Szutkowski Karolina Bossak-Ahmad Piotr Skrobecki Simon C. Drew Jarosław Poznański Igor Zhukov Tomasz Frączyk Wojciech Bal |
| author_facet | Mariusz Mital Kosma Szutkowski Karolina Bossak-Ahmad Piotr Skrobecki Simon C. Drew Jarosław Poznański Igor Zhukov Tomasz Frączyk Wojciech Bal |
| author_sort | Mariusz Mital |
| collection | DOAJ |
| description | The A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>42</mn></mrow></msub></semantics></math></inline-formula> peptide is a major beta-amyloid species in the human brain, forming toxic aggregates related to Alzheimer’s Disease. It also strongly chelates Cu(II) at the N-terminal Phe-Arg-His ATCUN motif, as demonstrated in A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>16</mn></mrow></msub></semantics></math></inline-formula> and A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>9</mn></mrow></msub></semantics></math></inline-formula> model peptides. The resulting complex resists ROS generation and exchange processes and may help protect synapses from copper-related oxidative damage. Structural characterization of Cu(II)A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mi>x</mi></mrow></msub></semantics></math></inline-formula> complexes by NMR would help elucidate their biological function, but is precluded by Cu(II) paramagneticism. Instead we used an isostructural diamagnetic Pd(II)-A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>16</mn></mrow></msub></semantics></math></inline-formula> complex as a model. To avoid a kinetic trapping of Pd(II) in an inappropriate transient structure, we designed an appropriate pH-dependent synthetic procedure for ATCUN Pd(II)A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>16</mn></mrow></msub></semantics></math></inline-formula>, controlled by CD, fluorescence and ESI-MS. Its assignments and structure at pH 6.5 were obtained by TOCSY, NOESY, ROESY, <inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>1</mn></msup></semantics></math></inline-formula>H-<inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>13</mn></msup></semantics></math></inline-formula>C HSQC and <inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>1</mn></msup></semantics></math></inline-formula>H-<inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>15</mn></msup></semantics></math></inline-formula>N HSQC NMR experiments, for natural abundance <inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>13</mn></msup></semantics></math></inline-formula>C and <inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>15</mn></msup></semantics></math></inline-formula>N isotopes, aided by corresponding experiments for Pd(II)-Phe-Arg-His. The square-planar Pd(II)-ATCUN coordination was confirmed, with the rest of the peptide mostly unstructured. The diffusion rates of A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>16</mn></mrow></msub></semantics></math></inline-formula>, Pd(II)-A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>16</mn></mrow></msub></semantics></math></inline-formula> and their mixture determined using PGSE-NMR experiment suggested that the Pd(II) complex forms a supramolecular assembly with the apopeptide. These results confirm that Pd(II) substitution enables NMR studies of structural aspects of Cu(II)-A<inline-formula><math display="inline"><semantics><mi>β</mi></semantics></math></inline-formula> complexes. |
| first_indexed | 2024-03-10T14:22:07Z |
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| id | doaj.art-251bf718d5f24a44a315dcf37f20c8d0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:22:07Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-251bf718d5f24a44a315dcf37f20c8d02023-11-20T23:16:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012123920010.3390/ijms21239200The Palladium(II) Complex of A<i>β</i><sub>4−16</sub> as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-AmyloidsMariusz Mital0Kosma Szutkowski1Karolina Bossak-Ahmad2Piotr Skrobecki3Simon C. Drew4Jarosław Poznański5Igor Zhukov6Tomasz Frączyk7Wojciech Bal8Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warszawa, PolandNanoBioMedical Centre, Adam Mickiewicz University, 61-614 Poznań, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warszawa, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warszawa, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warszawa, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warszawa, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warszawa, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warszawa, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warszawa, PolandThe A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>42</mn></mrow></msub></semantics></math></inline-formula> peptide is a major beta-amyloid species in the human brain, forming toxic aggregates related to Alzheimer’s Disease. It also strongly chelates Cu(II) at the N-terminal Phe-Arg-His ATCUN motif, as demonstrated in A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>16</mn></mrow></msub></semantics></math></inline-formula> and A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>9</mn></mrow></msub></semantics></math></inline-formula> model peptides. The resulting complex resists ROS generation and exchange processes and may help protect synapses from copper-related oxidative damage. Structural characterization of Cu(II)A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mi>x</mi></mrow></msub></semantics></math></inline-formula> complexes by NMR would help elucidate their biological function, but is precluded by Cu(II) paramagneticism. Instead we used an isostructural diamagnetic Pd(II)-A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>16</mn></mrow></msub></semantics></math></inline-formula> complex as a model. To avoid a kinetic trapping of Pd(II) in an inappropriate transient structure, we designed an appropriate pH-dependent synthetic procedure for ATCUN Pd(II)A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>16</mn></mrow></msub></semantics></math></inline-formula>, controlled by CD, fluorescence and ESI-MS. Its assignments and structure at pH 6.5 were obtained by TOCSY, NOESY, ROESY, <inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>1</mn></msup></semantics></math></inline-formula>H-<inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>13</mn></msup></semantics></math></inline-formula>C HSQC and <inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>1</mn></msup></semantics></math></inline-formula>H-<inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>15</mn></msup></semantics></math></inline-formula>N HSQC NMR experiments, for natural abundance <inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>13</mn></msup></semantics></math></inline-formula>C and <inline-formula><math display="inline"><semantics><msup><mrow></mrow><mn>15</mn></msup></semantics></math></inline-formula>N isotopes, aided by corresponding experiments for Pd(II)-Phe-Arg-His. The square-planar Pd(II)-ATCUN coordination was confirmed, with the rest of the peptide mostly unstructured. The diffusion rates of A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>16</mn></mrow></msub></semantics></math></inline-formula>, Pd(II)-A<inline-formula><math display="inline"><semantics><msub><mi>β</mi><mrow><mn>4</mn><mo>−</mo><mn>16</mn></mrow></msub></semantics></math></inline-formula> and their mixture determined using PGSE-NMR experiment suggested that the Pd(II) complex forms a supramolecular assembly with the apopeptide. These results confirm that Pd(II) substitution enables NMR studies of structural aspects of Cu(II)-A<inline-formula><math display="inline"><semantics><mi>β</mi></semantics></math></inline-formula> complexes.https://www.mdpi.com/1422-0067/21/23/9200Alzheimer’s diseaseAβ peptideNMR spectroscopy<sup>13</sup>C relaxationPalladium(II)ATCUN motif |
| spellingShingle | Mariusz Mital Kosma Szutkowski Karolina Bossak-Ahmad Piotr Skrobecki Simon C. Drew Jarosław Poznański Igor Zhukov Tomasz Frączyk Wojciech Bal The Palladium(II) Complex of A<i>β</i><sub>4−16</sub> as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids International Journal of Molecular Sciences Alzheimer’s disease Aβ peptide NMR spectroscopy <sup>13</sup>C relaxation Palladium(II) ATCUN motif |
| title | The Palladium(II) Complex of A<i>β</i><sub>4−16</sub> as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids |
| title_full | The Palladium(II) Complex of A<i>β</i><sub>4−16</sub> as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids |
| title_fullStr | The Palladium(II) Complex of A<i>β</i><sub>4−16</sub> as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids |
| title_full_unstemmed | The Palladium(II) Complex of A<i>β</i><sub>4−16</sub> as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids |
| title_short | The Palladium(II) Complex of A<i>β</i><sub>4−16</sub> as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids |
| title_sort | palladium ii complex of a i β i sub 4 16 sub as suitable model for structural studies of biorelevant copper ii complexes of n truncated beta amyloids |
| topic | Alzheimer’s disease Aβ peptide NMR spectroscopy <sup>13</sup>C relaxation Palladium(II) ATCUN motif |
| url | https://www.mdpi.com/1422-0067/21/23/9200 |
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