Multivalent fluorescent probes
Inventors
Singh, Rajendra • Zhang, Ning • Kim, Jae Beom • Diwu, Zhenjun
Assignees
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Publication Number
US-9012242-B2
Publication Date
2015-04-21
Expiration Date
Abstract
Multivalent fluorescent probes and methods of using these multivalent fluorescent probes for in vitro and in vivo imaging are described.
Core Innovation
The invention relates to multivalent fluorescent probes that include one fluorochrome emitting light in a wavelength range of 550 to 1200 nm. The probes are configured so that targeting moieties are linked through linkers to a defined probe structure, and the targeting moieties specifically target the multivalent fluorescent probe to a specific cell.
The linkers L1, L2, L3 and L4 comprise linear atoms selected from carbon, nitrogen, oxygen, phosphorus and sulfur, with substitution options including hydrogen, alkyl, alkoxy, trifluoromethyl, halogen, methylthio, sulfonyl, carbonyl, hydroxy, amino, thiol, amino acid residues, RGD, zinc (Zn), or a ligand that binds to a cell surface receptor. The targeting moieties include classes such as RGD, zinc-binding groups including DPA-Zn(2)/bis(zinc(II)-dicolylamine), and ligands that bind receptors, with illustrative target classes including glucose transport and COX-binding indomethacin.
The document further describes imaging and evaluation of disease-related targets using these multivalent fluorescent probes in both in vitro and in vivo contexts. It provides illustrative example compounds culminating in multivalent probes used in an example set, including imaging results showing improved tumor or bacterial specificity for multivalent constructs in mouse models and bacterial infection imaging contexts.
Claims Coverage
The provided claim set identifies one independent inventive feature focused on the structure and emission wavelength range of a multivalent fluorescent probe with multiple targeting moieties linked through specified linkers, and on the targeting specificity to a cell. Dependent claims refine the independent claim by constraining the relationships among the targeting moieties and by adding a kit embodiment.
Multivalent fluorescent probe with linked targeting moieties and 550 to 1200 nm emission
A multivalent fluorescent probe in which four targeting moieties are linked to X, Y, N and N+ via L1, L2, L3 and L4, where L1 to L4 comprise 10 to 50 linear atoms selected from carbon, nitrogen, oxygen, phosphorus and sulfur and are substituted by the listed substituents including RGD, zinc (Zn), or a ligand binding to a cell surface receptor; the probe emits light having a wavelength of 550 to 1200 nm; and the targeting moiety specifically targets the multivalent fluorescent probe to a specific cell.
The core inventive coverage is the multivalent fluorescent probe architecture with four linked targeting moieties, specified linker atom content and substitutions, and fluorescence emission in the 550 to 1200 nm range, with targeting specificity to a particular cell; dependent refinements address whether targeting moieties are the same or different, example categories of targeting-moiety types, and a kit embodiment.
Stated Advantages
Improved tumor or bacterial specificity for multivalent constructs, as shown in illustrative mouse imaging results.
Documented Applications
In vitro and in vivo detection and imaging using multivalent fluorescent probes for cell, tissue, and animal contexts and disease evaluation, including tumor model imaging results.
Bacterial infection imaging using multivalent fluorescent probes with examples including Pseudomonas aeruginosa and LPS-related targeting described in the provided content.
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