The PEG-fluorochrome shielding approach for targeted probe design.
The PEG-fluorochrome shielding approach for targeted probe design.
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DOI：
10.1021/ja309085b
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发表时间：
2012-11-28
影响因子：
15
通讯作者：
Josephson, Lee
中科院分区：
文献类型：
--
作者：
Guo, Yanyan;Yuan, Hushan;Rice, William L.;Kumar, Anand T. N.;Goergen, Craig J.;Jokivarsi, Kimmo;Josephson, Lee
我们提供了一种新的荧光探针设计方法，称为“PEG-荧光染料屏蔽”，其中PEG化提高量子产率，同时阻止荧光染料和生物分子之间的相互作用。为了证明PEG-荧光染料屏蔽，合成了携带荧光染料的肽探针，三个不含PEG，三个具有5 kDa PEG官能团。在体外，PEG阻断了荧光染料标记的肽探针彼此之间的相互作用（吸收光谱，自猝灭），并减少了与细胞的非特异性相互作用（通过FACS）。体内PEG阻断了与生物分子的相互作用，导致探针保留（通过表面荧光）。整合素体内靶向作为111 In标记的荧光染料屏蔽的整合素结合RGD和对照RAD探针的差异摄取获得。使用PEG来阻断荧光染料介导的相互作用，而不是从头合成荧光染料，可以产生用于设计主动或被动靶向的近红外荧光探针的新方法。
We provide a new approach for fluorescent probe design termed “PEG-fluorochrome Shielding,” where PEGylation enhances quantum yields while blocking troublesome interactions between fluorochromes and biomolecules. To demonstrate PEG-fluorochrome shielding, fluorochrome-bearing peptide probes were synthesized, three without PEG and three with a 5 kDa PEG functional group. In vitro, PEG blocked the interactions of fluorochrome-labeled peptide probes with each other (absorption spectra, self-quenching) and reduced nonspecific interactions with cells (by FACS). In vivo PEG blocked interactions with biomolecules that lead to probe retention (by surface fluorescence). Integrin targeting in vivo was obtained as the differential uptake of an 111In labeled, fluorochrome shielded, integrin binding RGD and control RAD probes. Using PEG to block fluorochrome mediated interactions, rather than synthesizing de novo fluorochromes, can yield new approaches for the design of actively or passively targeted near infrared fluorescent probes.
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