Chilla Satya Narayana Murthy, Zemek Ondrej, Kotek Jan, Boutry Sébastien, Larbanoix Lionel, Sclavons Coralie, Elst Luce Vander, Lukes Ivan, Muller Robert N, Laurent Sophie
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau, 19, Mendeleïev Building, 7000 Mons, Belgium.
Department of Inorganic Chemistry, Universita Karlova, Hlavova 2030, 128 40 Prague 2, Czech Republic.
Bioorg Med Chem. 2017 Aug 15;25(16):4297-4303. doi: 10.1016/j.bmc.2017.06.008. Epub 2017 Jun 15.
A new facile synthetic strategy was developed to prepare bifunctional monophosphinic acid Ln-DOTA derivatives, Gd-DO2AGAP and Gd- DO2AGAP. The relaxivities of the Gd-complexes are enhanced compared to Gd-DOTA. Monophosphinic acid arm of these Gd-complexes affords enhancement of inner sphere water exchange rate due to its steric bulkiness. The different functionalities of DO2AGAP were appended in trans positions and are designed to conjugate identical or different vectors according to the potential applications. The conjugation of Gd-DO2AGAP with E3 peptide known to target apoptosis was successfully performed and in vivo MRI allowed cell death detection in a mouse model.
开发了一种新的简便合成策略来制备双功能单膦酸镧系元素-DOTA衍生物，即钆-DO2AGAP和钆-DO2AGAP。与钆-DOTA相比，钆配合物的弛豫率有所提高。这些钆配合物的单膦酸臂由于其空间体积大，提高了内球水交换速率。DO2AGAP的不同功能基团连接在反式位置，并根据潜在应用设计用于连接相同或不同的载体。成功地将钆-DO2AGAP与已知靶向细胞凋亡的E3肽进行了缀合，体内磁共振成像能够在小鼠模型中检测细胞死亡。
