通过连接一种黑素皮质素 1 受体 (MC1R) 特异性配体来开发黑色素瘤靶向聚合物胶束。
Development of melanoma-targeted polymer micelles by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.
机构信息
Department of Imaging, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, United States.
出版信息
J Med Chem. 2011 Dec 8;54(23):8078-84. doi: 10.1021/jm201226w. Epub 2011 Nov 10.
Abstract
The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. Because of its high expression on the surface of melanomas, MC1R has been investigated as a target for selective imaging and therapeutic agents against melanoma. Eight ligands were screened against cell lines engineered to overexpress MC1R, MC4R, or MC5R. Of these, compound 1 (4-phenylbutyryl-His-dPhe-Arg-Trp-NH(2)) exhibited high (0.2 nM) binding affinity for MC1R and low (high nanomolar) affinities for MC4R and MC5R. Functionalization of the ligand at the C-terminus with an alkyne for use in Cu-catalyzed click chemistry was shown not to affect the binding affinity. Finally, formation of the targeted polymer, as well as the targeted micelle formulation, also resulted in constructs with low nanomolar binding affinity.
摘要
在美国，恶性黑色素瘤的发病率上升速度比其他任何癌症都要快。由于 MC1R 在黑色素瘤表面的高表达，它已被研究作为针对黑色素瘤的选择性成像和治疗剂的靶标。筛选了八种配体来针对过表达 MC1R、MC4R 或 MC5R 的细胞系。其中，化合物 1（4-苯丁酰基-His-dPhe-Arg-Trp-NH（2））对 MC1R 表现出高（0.2 nM）结合亲和力，对 MC4R 和 MC5R 的亲和力较低（高纳摩尔）。在 C 末端将配体功能化，接上一个炔基以用于铜催化的点击化学，这并不会影响结合亲和力。最后，靶向聚合物的形成以及靶向胶束制剂也导致构建体具有低纳摩尔的结合亲和力。
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