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A chemically stable fluorescent marker of the ureter
Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2018-02-24 , DOI: 10.1016/j.bmcl.2018.02.040
Jaepyeong Cha , Roger R. Nani , Michael P. Luciano , Gabriel Kline , Aline Broch , Kihoon Kim , Jung-Man Namgoong , Rhushikesh A. Kulkarni , Jordan L. Meier , Peter Kim , Martin J. Schnermann

Surgical methods guided by exogenous fluorescent markers have the potential to define tissue types in real time. Small molecule dyes with efficient and selective renal clearance could enable visualization of the ureter during surgical procedures involving the abdomen and pelvis. These studies report the design and synthesis of a water soluble, net neutral C4′-O-alkyl heptamethine cyanine, Ureter-Label (UL)-766, with excellent properties for ureter visualization. This compound is accessed through a concise synthetic sequence involving an N- to O-transposition reaction that provides other inaccessible C4′-O-alkyl heptamethine cyanines. Unlike molecules containing a C4′-O-aryl substituent, which have also been used for ureter visualization, UL-766 is not reactive towards glutathione and the cellular proteome. In addition, rat models of abdominal surgery reveal that UL-766 undergoes efficient and nearly exclusive renal clearance in vivo. In total, this molecule represents a promising candidate for visualizing the ureter during a variety of surgical interventions.



中文翻译:

输尿管的化学稳定的荧光标记

由外源性荧光标记物指导的手术方法具有实时定义组织类型的潜力。具有有效和选择性肾脏清除功能的小分子染料可以在涉及腹部和骨盆的外科手术过程中使输尿管可视化。这些研究报告了水溶性和纯净的中性C4'- O-烷基七甲meth菁花色素输尿管标签(UL)-766的设计和合成,具有出色的输尿管可视化性能。该化合物可通过简明的合成序列来获得,该合成序列涉及从N-O-换位反应,该反应提供了其他难以接近的C4'- O-烷基七甲胺花菁。不像含有C4'- O-的分子芳基取代基(也已用于输尿管可视化),UL-766对谷胱甘肽和细胞蛋白质组没有反应。另外,大鼠腹部手术模型显示UL-766在体内经历有效且几乎排他的肾脏清除。总体而言,该分子代表了在各种外科手术过程中可视化输尿管的有希望的候选物。

更新日期:2018-02-24
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