Multi-color time resolved fluorophores based on macrocyclic lanthanide complexes
AssigneeLumiphore, Inc.
InventorsNathaniel G. Butlin, Todd M. Corneillie, Jide Xu
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Abstract
The present invention provides a novel class of macrocyclic compounds as well as complexes formed between a metal (e.g., lanthanide) ion and the compounds of the invention. Preferred complexes exhibit high stability as well as high quantum yields of lanthanide ion luminescence in aqueous media without the need for secondary activating agents. Preferred compounds incorporate hydroxy-isophthalamide moieties within their macrocyclic structure and are characterized by surprisingly low, non-specific binding to a variety of polypeptides such as antibodies and proteins as well as high kinetic stability. These characteristics distinguish them from known, open-structured ligands.
Claims25
A compound having a structure according to Formula I:
- wherein
- each Z is a member independently selected from O and S;
- L1, L2, L3, L4, L5, L6, L7, L8, L9 and L10 are linker groups independently selected from substituted or unsubstituted C1 to C6 alkyl;
- A1, A2, A3 and A4 are members independently selected from the general structure:
- wherein
- each R1 is a member independently selected from H, an enzymatically labile group, a hydrolytically labile group, a metabolically labile group and a single negative charge;
- and
- each R5, R6 and R7 is a member independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, halogen, CN, CF3, acyl, —SO2NR17R18, —NR17R18, —OR17, —S(O)2R17, —COOR17, —S(O)2OR17, —OC(O)R17, —C(O)NR17R18, —NR17C(O)R18, —NR17SO2R18, and NO2,
- wherein
- R6 and a member selected from R5, R7 and combinations thereof are optionally joined to form a ring system which is a member selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;
- and
- R17 and R18 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocycloalkyl, and R17 and R18, together with the atoms to which they are attached, are optionally joined to form a 5- to 7-membered ring;
- and
- wherein at least one moiety selected from L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 is substituted with:
- wherein
- LF is an acceptor-linker;
- F is a fluorophore bound to LF through a linkage fragment;
- and
- FM is a functional moiety,
- wherein said functional moiety comprises a reactive functional group, or said functional moiety is bound to a carrier moiety or solid support through a linkage fragment.
Dependencies are inferred from the claim text.