Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes

被引:108
作者
Licha, K [1 ]
Hessenius, C
Becker, A
Henklein, P
Bauer, M
Wisniewski, S
Wiedenmann, B
Semmler, W
机构
[1] Free Univ Berlin, Inst Diagnost Forsch GmbH, D-14050 Berlin, Germany
[2] Humboldt Univ, Charite Med Sch, Dept Internal Med, Div Gastroenterol & Hepatol, D-13353 Berlin, Germany
[3] Humboldt Univ, Inst Biochem, D-10115 Berlin, Germany
关键词
D O I
10.1021/bc000040s
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We present the synthesis and characterization of the somatostatin receptor-specific peptide H2N-(D-Phe)-cyclo[Cys-Phe-(D-Trp)-Lys-Thr-Cys]-Thr-OH which is labeled with a carboxylated indodicarbo and an indotricarbocyanine dye at the N-terminal amino group. The preparation was performed by automated solid-phase synthesis, with subsequent attachment of the cyanine dye and cleavage of the entire conjugate from the resin. The compounds display high molar absorbance and fluorescence quantum yields typical for cyanine dyes and are thus suitable receptor-targeted contrast agents for molecular optical imaging. The ability of these agents to target the somatostatin receptor was demonstrated by flow cytometry in vitro, in which the indotricarbocyanine conjugate led to elevated cell-associated fluorescence on somatostatin receptor-expressing tumor cells. In contrast, the corresponding linearized derivative of the sequence H2N-(D-Phe)-Met-Phe-(D-Trp)-Lys-Thr-Met-Thr-OH produced only minimal cell fluorescence, hence confirming the specificity of the cyclic somatostatin analogue. Intracellular localization could be visualized by near-infrared (NIR) fluorescence microscopy. In conclusion, receptor-specific peptides are promising tools for designing site-directed optical contrast agents for use in molecular optical imaging.
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页码:44 / 50
页数:7
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