Dataset Information

In situ imaging of quantum dot-AZD4547 conjugates for tracking the dynamic behavior of fibroblast growth factor receptor 3.

ABSTRACT: Fibroblast growth factor receptors (FGFRs) play an important role in determining cell proliferation, differentiation, migration, and survival. Although a variety of small-molecule FGFR inhibitors have been developed for cancer therapeutics, the interaction between FGFRs and FGFR inhibitors has not been well characterized. The FGFR-inhibitor interaction can be characterized using a new imaging probe that has strong, stable signal properties for in situ cellular imaging of the interaction without quenching. We developed a kinase-inhibitor-modified quantum dot (QD) probe to investigate the interaction between FGFR and potential inhibitors. Especially, turbo-green fluorescent protein-FGFR3s were overexpressed in HeLa cells to investigate the colocalization of FGFR3 and AZD4547 using the QD-AZD4547 probe. The result indicates that this probe is useful for investigating the binding behaviors of FGFR3 with the FGFR inhibitor. Thus, this new inhibitor-modified QD probe is a promising tool for understanding the interaction between FGFR and inhibitors and for creating future high-content, cell-based drug screening strategies.

SUBMITTER: Hwang G

PROVIDER: S-EPMC5536236 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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In situ imaging of quantum dot-AZD4547 conjugates for tracking the dynamic behavior of fibroblast growth factor receptor 3.

Hwang Gyoyeon G Kim Hyeonhye H Yoon Hojong H Song Chiman C Lim Dong-Kwon DK Sim Taebo T Lee Jiyeon J

International journal of nanomedicine 20170726

Fibroblast growth factor receptors (FGFRs) play an important role in determining cell proliferation, differentiation, migration, and survival. Although a variety of small-molecule FGFR inhibitors have been developed for cancer therapeutics, the interaction between FGFRs and FGFR inhibitors has not been well characterized. The FGFR-inhibitor interaction can be characterized using a new imaging probe that has strong, stable signal properties for in situ cellular imaging of the interaction without ...[more]

PMID: 28794627

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Project description:Highly fluorescent CdSe quantum dots (qdots) can serve as a platform for tethering multiple copies of a receptor-targeted ligand, affording study of how the level of multivalency affects receptor binding. We previously showed that qdots conjugated with long PEG chains terminated by muscimol, a known GABA(C) agonist, exhibit specific binding to the surface membrane of GABA(C) receptor-expressing Xenopus oocytes. The present report addresses the effect of varying the number, i.e., valency, of muscimol- (M-) terminated PEG chains attached to the qdot on binding of the resulting conjugate to GABA(C) receptors. M-PEG-qdots of differing muscimol valency were prepared by conjugating AMP-CdSe/ZnS qdots with muscimol-terminated and methylamine-terminated PEG chains in proportions designed to yield varying percentages of muscimol-terminated chains among the total approximately 150-200 chains bound to the qdot. The investigated valencies represented 0%, approximately 25%, approximately 50%, and 100% loading with muscimol (preparations termed M-PEG-qdot0, M-PEG-qdot25, M-PEG-qdot50, and M-PEG-qdot100, respectively. Binding of a given conjugate to surface membranes of GABA(C) receptor-expressing oocytes was analyzed by quantitative fluorescence microscopy following defined incubation with approximately 30 nM of the conjugate. With 5-20 min incubation, the fluorescence signal resulting from incubation with M-PEG-qdot25 exceeded, by approximately 6-fold, the fluorescence level obtained with M-PEG-qdot preparations that lacked muscimol-terminated chains (M-PEG-qdot0). M-PEG-qdot50 yielded a net signal roughly similar to that of M-PEG-qdot25, and that produced by M-PEG-qdot100 exceeded, by approximately 30-50%, those for M-PEG-qdot25 and M-PEG-qdot50. The time course of changes in oocyte surface membrane fluorescence resulting from the introduction of and removal of M-PEG-qdots in the medium bathing the oocyte indicated only a modest dependence of both binding and wash-out kinetics on muscimol valency. The results demonstrate a dependence of the binding activity of the M-PEG-qdot conjugates on muscimol valency, presumably reflecting higher GABA(C) avidity and/or affinity of the muscimol at high valency, and provide insight on the interactions of membrane receptor proteins with qdot conjugates containing multiple copies of a receptor-targeting ligand.

Dataset Information

In situ imaging of quantum dot-AZD4547 conjugates for tracking the dynamic behavior of fibroblast growth factor receptor 3.

Publications

In situ imaging of quantum dot-AZD4547 conjugates for tracking the dynamic behavior of fibroblast growth factor receptor 3.

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