Development of melanoma-targeted polymer micelles by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.
Development of melanoma-targeted polymer micelles by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.
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DOI：
10.1021/jm201226w
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发表时间：
2011-12-08
影响因子：
7.3
通讯作者：
Vagner, Josef
中科院分区：
文献类型：
--
作者：
Barkey, Natalie M.;Tafreshi, Narges K.;Josan, Jatinder S.;De Silva, Channa R.;Sill, Kevin N.;Hruby, Victor J.;Gillies, Robert J.;Morse, David L.;Vagner, Josef
在美国，恶性黑色素瘤的发病率比任何其他癌症的发病率都上升得快。由于其在黑色素瘤表面的高表达，MC 1 R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。针对工程化以过表达MC 1 R、MC 4 R或MC 5 R的细胞系筛选八种配体。其中，化合物1（4-苯基丁酰-His-Dphe-Arg-Trp-NH 2）对MC 1 R表现出高（0.2nM）结合亲和力，对MC 4 R和MC 5 R表现出低（高nM）亲和力。随后，在C-末端用炔官能化配体用于Cu催化的点击化学显示不影响结合亲和力。最后，靶向聚合物以及靶向胶束制剂的形成也导致具有低nM结合亲和力的构建体。
The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. Due to 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 over-express MC1R, MC4R or MC5R. Of these, compound 1 (4-phenylbutyryl-His-Dphe-Arg-Trp-NH2) exhibited high (0.2 nM) binding affinity for MC1R, and low (high nM) affinities for MC4R and MC5R. Subsequently 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 nM binding affinity.
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DOI：
10.1073/pnas.77.10.5754
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
SAWYER, TK;SANFILIPPO, PJ;HADLEY, ME
通讯作者：
HADLEY, ME
影响因子：
4.1
作者：
Fridmanis, Davids;Petrovska, Ramona;Klovins, Janis
通讯作者：
Klovins, Janis
影响因子：
7.3
作者：
Cai, MY;Mayorov, AV;Hruby, VJ
通讯作者：
Hruby, VJ
影响因子：
2.7
作者：
Koikov, LN;Ebetino, FH;Knittel, JJ
通讯作者：
Knittel, JJ
影响因子：
4.7
作者：
Handl, Heather L.;Sankaranarayanan, Rajesh;Hruby, Victor J.
通讯作者：
Hruby, Victor J.