Cisbio Bioassays, Parc Marcel Boiteux, BP 84175 30200, Codolet, France.
Org Biomol Chem. 2012 Nov 14;10(42):8509-23. doi: 10.1039/c2ob26311d. Epub 2012 Sep 25.
The convenient and efficient synthesis of two macrocyclic ligands (15- and 18-membered) based on a dipyrido-6,7,8,9-tetrahydrophenazine (dpqc) or 2,2':6',2''-terpyridine (tpy) heterocycle and a DTTA (diethylenetriaminetriacetic acid) skeleton is described. In these ligands the DTTA skeleton contains an additional extracyclic functionality (NH(2) group) suitable for covalent attachment to bioactive molecules. These octa- and nonadentate ligands form very stable and luminescent neutral lanthanide complexes in aqueous solutions at physiological pH. The corresponding Eu(III) and Tb(III) complexes are characterized by a maximum absorption wavelength compatible with nitrogen laser excitation (337 nm) and attractive lifetimes and quantum yields. Further introduction of a maleimide bioconjugatable handle in the Eu(III) complexes was investigated and a valuable luminescence brightness above 1500 dm(3) mol(-1) cm(-1) at 337 nm was obtained with the corresponding Eu(III) tpy-derivative. Finally, these two luminescent chelates were grafted onto thiol residues of a model antibody (Mab GSS11) without loss of their luminescent properties.
基于二吡啶并[6,7,8,9-四氢吩嗪（dpqc）或 2,2':6',2''-三联吡啶（tpy）杂环和 DTTA（二乙三胺五乙酸）骨架，方便有效地合成了两种大环配体（15 元和 18 元）。在这些配体中，DTTA 骨架包含一个额外的外环官能团（NH(2)基团），适合与生物活性分子共价连接。这些八齿和非齿配位体在生理 pH 值的水溶液中形成非常稳定和发光的中性镧系元素配合物。相应的 Eu(III) 和 Tb(III) 配合物的最大吸收波长与氮气激光激发（337nm）兼容，具有吸引人的寿命和量子产率。进一步研究了在 Eu(III) 配合物中引入马来酰亚胺可生物偶联的接头，并获得了相应的 Eu(III) tpy 衍生物，其在 337nm 处的发光亮度超过 1500dm(3)mol(-1)cm(-1)。最后，将这两种发光螯合物接枝到模型抗体（Mab GSS11）的巯基残基上，而不损失其发光性质。
