Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi, 110054, India.
Chem Biol Drug Des. 2013 Aug;82(2):226-32. doi: 10.1111/cbdd.12147.
Catecholamine mimetic EDTA-bis(tyramide) was synthesized and characterized by various spectroscopic techniques (NMR, mass spectroscopy) and λem 310 nm for the excitation at 270 nm. Molecular docking studies were performed with human serum albumin (PDB 1E78), showing binding pattern with amino acid residues Arg218, Arg222, and Lys444, identifies the ligand-human serum albumin interaction for the transportation affinity of the ligand at the specific site of the target. Subsequently, binding study with human serum albumin at λex = 350 nm found to be 5.847 × 10(4) m(-1) shows effective quenching effect. Additionally, to go more insight, acetylcholinesterase binding affinity was investigated, which shows 90% binding affinity for the 10 mm concentration. IC50 value was found 18.60 μm for MAO-B inhibition. Finally, EDTA-bis(tyramide) labeled with (99m) Tc to investigate its in vivo radiopharmaceutical efficiency having 97% binding affinity with 98% radiochemical purity. In vivo studies were carried out for (99m) Tc-EDTA-bis(tyramide) included blood kinetics showed a quick wash out from the circulation via renal route, and biodistribution revealed that maximum %ID/g was found in kidney at 1 h, and its scintigraphy image shows 3.96% brain uptake with respect to whole body.
合成了儿茶酚胺模拟物 EDTA-双（酪胺），并通过各种光谱技术（NMR、质谱）进行了表征，λem 为 310nm，激发波长为 270nm。进行了与人类血清白蛋白（PDB 1E78）的分子对接研究，显示与氨基酸残基 Arg218、Arg222 和 Lys444 的结合模式，确定了配体-人类血清白蛋白相互作用，以确定配体在靶标特定部位的运输亲和力。随后，在 λex = 350nm 时与人类血清白蛋白的结合研究发现，结合常数为 5.847×10(4)m(-1)，表现出有效的猝灭效应。此外，为了更深入地了解，研究了乙酰胆碱酯酶的结合亲和力，发现对于 10mm 浓度的结合亲和力为 90%。MAO-B 抑制的 IC50 值为 18.60μm。最后，用 (99m)Tc 标记 EDTA-双（酪胺），以研究其体内放射性药物效率，其与 98%放射性化学纯度的结合亲和力为 97%。进行了 (99m)Tc-EDTA-双（酪胺）的体内研究，包括血液动力学研究表明，其通过肾脏途径迅速从循环中清除，生物分布显示，在 1 小时时，肾脏的最大 %ID/g，其闪烁显像图像显示相对于全身，大脑摄取率为 3.96%。
