期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 53, 期 41, 页码 10975-10978出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201406842
关键词
activity-based protein profiling; drug delivery; endolysosomal pathway; fluorescent probes; mannose-6-phosphate
资金
- Netherlands Organization for Scientific Research (NWO-CW)
- European Research Council
The ubiquitously expressed mannose-6-phosphate receptors (MPRs) are a promising class of receptors for targeted compound delivery into the endolysosomal compartments of a variety of cell types. The development of a synthetic, multivalent, mannose-6-phosphate (M6P) glycopeptide-based MPR ligand is described. The conjugation of this ligand to fluorescent DCG-04, an activity-based probe for cysteine cathepsins, enabled fluorescent readout of its receptor-targeting properties. The resulting M6P-cluster-BODIPY-DCG-04 probe was shown to efficiently label cathepsins in cell lysates as well as in live cells. Furthermore, the introduction of the 6-O-phosphates leads to a completely altered uptake profile in COS and dendritic cells compared to a mannose-containing ligand. Competition with mannose-6-phosphate abolished all uptake of the probe in COS cells, and we conclude that the mannose-6-phosphate cluster targets the MPR and ensures the targeted delivery of cargo bound to the cluster into the endolysosomal pathway.
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