How do HYNIC-conjugated peptides bind technetium? Insights from LC-MS and stability studies.
How do HYNIC-conjugated peptides bind technetium? Insights from LC-MS and stability studies.
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DOI：
10.1039/b705111e
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发表时间：
2007-11-21
期刊：
影响因子：
--
通讯作者：
Mather SJ
中科院分区：
文献类型：
--
作者：
King RC;Surfraz MB;Biagini SC;Blower PJ;Mather SJ
肼烟酰胺（HYNIC）是一种已建立的双功能络合剂，但其配位球结构尚不确定。为了进一步了解这一点，我们用模型肽制备了HYNIC和肼苯甲酸（HYBA）的偶联物，并使用三种已建立的共配体体系：EDDA、三嗪和三嗪-烟酸，用99mTc对它们进行放射性标记。通过LC-MS和血清稳定性及蛋白结合试验对标记肽进行研究。对于每个共配体体系，HYNIC缀合物形成的标记种比对应的HYBA缀合物更少且更稳定。LC-MS分析表明，所有缀合物都含有一个与Tc结合的联氨基团，Tc与hynic肽和共配体的结合发生在5H+的位移中，表明Tc的形式氧化态为+5，Tc没有氧或卤化物配体。LC-MS还显示，HYNIC缀合物比HYBA缀合物含有更少的配位共配体分子，这表明HYNIC能够更有效地满足锝的配位要求，可能是通过螯合方式结合。
Hydrazinonicotinamide (HYNIC) is an established bifunctional complexing agent for technetium-99m (99mTc) but the structure of the technetium coordination sphere remains uncertain. To gain further insight into this, we have prepared conjugates of HYNIC and hydrazinobenzoic acid (HYBA) with a model peptide, and radiolabelled them with 99mTc using three well-established co-ligand systems: EDDA, tricine and tricine–nicotinic acid. The labelled peptides were studied by LC-MS and by subjecting them to serum stability and protein binding assays. For each co-ligand system, HYNIC conjugates formed fewer and more stable labelled species than the corresponding HYBA conjugates. LC-MS analysis showed that all conjugates contained one hydrazine moiety bound to Tc, that binding of Tc to HYNIC–peptide and co-ligand occurs with displacement of 5H+ indicating a Tc formal oxidation state of +5, and that the Tc has no oxo- or halide ligands. LC-MS also shows that complexes formed with the HYNIC conjugate contain fewer coordinating co-ligand molecules than the HYBA conjugate indicating that HYNIC is able to more effectively satisfy the coordination requirement of technetium, perhaps by binding in chelating mode.
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