Lanthanide DO3A-Complexes Bearing Peptide Substrates: The Effect of Peptidic Side Chains on Metal Coordination and Relaxivity
Two DO3A-type ligands conjugated to substrates of urokinase (L3) and caspase-3 (L4) via a propyl-amide linker were synthesized and their lanthanide(III) (Ln<sup>3+</sup>) complexes studied. A model compound without peptide substrate (L2) and an amine derivative ligand mimicking the state...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/8/2176 |
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| author | Sophie Laine Jean-François Morfin Mathieu Galibert Vincent Aucagne Célia S. Bonnet Éva Tóth |
| author_facet | Sophie Laine Jean-François Morfin Mathieu Galibert Vincent Aucagne Célia S. Bonnet Éva Tóth |
| author_sort | Sophie Laine |
| collection | DOAJ |
| description | Two DO3A-type ligands conjugated to substrates of urokinase (L3) and caspase-3 (L4) via a propyl-amide linker were synthesized and their lanthanide(III) (Ln<sup>3+</sup>) complexes studied. A model compound without peptide substrate (L2) and an amine derivative ligand mimicking the state after enzymatic cleavage (L1) were also prepared. Proton Nuclear Magnetic Relaxation Dispersion (NMRD) profiles recorded on the gadolinium(III) (Gd<sup>3+</sup>) complexes, complemented with the assessment of hydration numbers via luminescence lifetime measurements on the Eu<sup>3+</sup> analogues, allowed us to characterize the lanthanide coordination sphere in the chelates. These data suggest that the potential donor groups of the peptide side chains (carboxylate, amine) interfere in metal coordination, leading to non-hydrated LnL3 and LnL4 complexes. Nevertheless, GdL3 and GdL4 retain a relatively high relaxivity due to an important second-sphere contribution generated by the strongly hydrophilic peptide chain. Weak PARACEST effects are detected for the amine-derivative EuL1 and NdL1 chelates. Unfortunately, the GdL3 and GdL4 complexes are not significantly converted by the enzymes. The lack of enzymatic recognition of these complexes can likely be explained by the participation of donor groups from the peptide side chain in metal coordination. |
| first_indexed | 2024-03-10T12:28:05Z |
| format | Article |
| id | doaj.art-86616a63cf2f461098ff3b4d296837ce |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:28:05Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-86616a63cf2f461098ff3b4d296837ce2023-11-21T14:55:02ZengMDPI AGMolecules1420-30492021-04-01268217610.3390/molecules26082176Lanthanide DO3A-Complexes Bearing Peptide Substrates: The Effect of Peptidic Side Chains on Metal Coordination and RelaxivitySophie Laine0Jean-François Morfin1Mathieu Galibert2Vincent Aucagne3Célia S. Bonnet4Éva Tóth5Centre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, CEDEX 2, 45071 Orléans, FranceCentre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, CEDEX 2, 45071 Orléans, FranceCentre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, CEDEX 2, 45071 Orléans, FranceCentre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, CEDEX 2, 45071 Orléans, FranceCentre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, CEDEX 2, 45071 Orléans, FranceCentre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, CEDEX 2, 45071 Orléans, FranceTwo DO3A-type ligands conjugated to substrates of urokinase (L3) and caspase-3 (L4) via a propyl-amide linker were synthesized and their lanthanide(III) (Ln<sup>3+</sup>) complexes studied. A model compound without peptide substrate (L2) and an amine derivative ligand mimicking the state after enzymatic cleavage (L1) were also prepared. Proton Nuclear Magnetic Relaxation Dispersion (NMRD) profiles recorded on the gadolinium(III) (Gd<sup>3+</sup>) complexes, complemented with the assessment of hydration numbers via luminescence lifetime measurements on the Eu<sup>3+</sup> analogues, allowed us to characterize the lanthanide coordination sphere in the chelates. These data suggest that the potential donor groups of the peptide side chains (carboxylate, amine) interfere in metal coordination, leading to non-hydrated LnL3 and LnL4 complexes. Nevertheless, GdL3 and GdL4 retain a relatively high relaxivity due to an important second-sphere contribution generated by the strongly hydrophilic peptide chain. Weak PARACEST effects are detected for the amine-derivative EuL1 and NdL1 chelates. Unfortunately, the GdL3 and GdL4 complexes are not significantly converted by the enzymes. The lack of enzymatic recognition of these complexes can likely be explained by the participation of donor groups from the peptide side chain in metal coordination.https://www.mdpi.com/1420-3049/26/8/2176lanthanideMRI contrast agentspeptideenzymatic detection |
| spellingShingle | Sophie Laine Jean-François Morfin Mathieu Galibert Vincent Aucagne Célia S. Bonnet Éva Tóth Lanthanide DO3A-Complexes Bearing Peptide Substrates: The Effect of Peptidic Side Chains on Metal Coordination and Relaxivity Molecules lanthanide MRI contrast agents peptide enzymatic detection |
| title | Lanthanide DO3A-Complexes Bearing Peptide Substrates: The Effect of Peptidic Side Chains on Metal Coordination and Relaxivity |
| title_full | Lanthanide DO3A-Complexes Bearing Peptide Substrates: The Effect of Peptidic Side Chains on Metal Coordination and Relaxivity |
| title_fullStr | Lanthanide DO3A-Complexes Bearing Peptide Substrates: The Effect of Peptidic Side Chains on Metal Coordination and Relaxivity |
| title_full_unstemmed | Lanthanide DO3A-Complexes Bearing Peptide Substrates: The Effect of Peptidic Side Chains on Metal Coordination and Relaxivity |
| title_short | Lanthanide DO3A-Complexes Bearing Peptide Substrates: The Effect of Peptidic Side Chains on Metal Coordination and Relaxivity |
| title_sort | lanthanide do3a complexes bearing peptide substrates the effect of peptidic side chains on metal coordination and relaxivity |
| topic | lanthanide MRI contrast agents peptide enzymatic detection |
| url | https://www.mdpi.com/1420-3049/26/8/2176 |
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