Design and Synthesis of Cathepsin-K-Activated Osteoadsorptive Fluorogenic Sentinel (OFS) Probes for Detecting Early Osteoclastic Bone Resorption in a Multiple Myeloma Mouse Model.
Design and Synthesis of Cathepsin-K-Activated Osteoadsorptive Fluorogenic Sentinel (OFS) Probes for Detecting Early Osteoclastic Bone Resorption in a Multiple Myeloma Mouse Model.
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DOI：
10.1021/acs.bioconjchem.1c00036
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发表时间：
2021-05-19
影响因子：
4.7
通讯作者：
McKenna CE
中科院分区：
文献类型：
--
作者：
Richard ET;Morinaga K;Zheng Y;Sundberg O;Hokugo A;Hui K;Zhou Y;Sasaki H;Kashemirov BA;Nishimura I;McKenna CE
We describe the design and synthesis of OFS-1, an Osteoadsorptive Fluorogenic Sentinel imaging probe that is adsorbed by hydroxyapatite (HAp) and bone mineral surfaces, where it generates an external fluorescent signal in response to osteoclast-secreted cathepsin K (Ctsk). The probe consists of a bone-anchoring bisphosphonate moiety connected to a Förster resonance energy transfer (FRET) internally quenched fluorescent (IQF) dye pair, linked by a Ctsk peptide substrate, GHPGGPQG. Key structural features contributing to the effectiveness of OFS-1 were defined by SAR and modeling studies comparing OFS-1 with two cognates, OFS-2 and OFS-3. In solution or when pre-adsorbed on HAp, OFS-1 exhibited strong fluorescence when exposed to Ctsk (2.5–20 nM). Time-lapse photomicrographs obtained after seeding human osteoclasts onto HAp-coated well plates containing pre-adsorbed OFS-1 revealed bright fluorescence at the periphery of resorbing cells. OFS-1 administered systemically detected early osteolysis co-localized with orthotopic engraftment of RPMI-8226-Luc human multiple myeloma cells at a metastatic skeletal site in a humanized mouse model. OFS-1 is thus a promising new imaging tool for detecting abnormal bone resorption.
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影响因子：
16.6
作者：
Hyun, Hoon;Wada, Hideyuki;Bao, Kai;Gravier, Julien;Yadav, Yogesh;Laramie, Matt;Henary, Maged;Frangioni, John V.;Choi, Hak Soo
通讯作者：
Choi, Hak Soo
影响因子：
15
作者：
Bhushan KR;Misra P;Liu F;Mathur S;Lenkinski RE;Frangioni JV
通讯作者：
Frangioni JV
影响因子：
1.9
作者：
Derlin, Thorsten;Bannas, Peter
通讯作者：
Bannas, Peter
影响因子：
1.2
作者：
Gastelum, Gilbert;Chang, Eric Y.;Frost, Patrick
通讯作者：
Frost, Patrick
DOI：
10.1186/bcr2835
发表时间：
2011-04-06
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Clézardin P
通讯作者：
Clézardin P