Heteroarylcyanine dyes with sulfonic acid substituents

摘要

Heteroaryl cyanine dyes bearing sulfonic acid substituents are of use in various assays, including single molecule nucleic acid sequencing. Exemplary heteroaryl cyanines dyes include or more reactive functional group, which is of use to covalently conjugate the cyanine dye to a carrier molecule. An exemplary carrier molecule is an analyte molecule or other molecule of interest, for example, a nucleotide oligophosphate.

主权项

1. A fluorescent cyanine compound, or a covalent conjugate thereof, having a formula selected from: wherein
R1, R2 and R3 are independently CH2R7;wherein
R4, R5, R6, R6′, and R7 are members independently selected from H, R28, R28Z2, SO3H, CO2H, R28SO3H, C(O)NHR28SO3H, CONHR28C(O)Z2, wherein
Z2 is selected from OH, O—, a reactive functional group, and a linker covalently bound to a carrier molecule;Rg1 and Rg2 are members independently selected from H, R38, R38Z3, SO3H, CO2H, R38SO3H, CONHR38SO3H, CONHR38C(O)Z2,wherein R28 and R38 are independently selected from a bond, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocycloalkyl; Z3 is selected from OH, O—, a reactive functional group, and a linker covalently bound to a carrier molecule;wherein
R1′, R2′ and R3′ are independently CH2R7′;wherein
R4′, R5′, and R7′ are members independently selected from H, R28′, R28′Z2′, SO3H, CO2H, R28′SO3H, CONHR28′SO3H, CONHR28′C(O)Z2′, and wherein
Z2′ is selected from OH, O—, a reactive functional group, and a linker covalently bound to a carrier molecule;Rg1′ and Rg2′ are members independently selected from H, R38′, R38′Z3′, SO3H, CO2H, R38′SO3H, CONHR38′SO3H, CONHR38′C(O)Z3′,wherein R28′ and R38′ are independently selected from a bond, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocycloalkyl; and Z3′ is selected from OH, O—, a reactive functional group, and a linker covalently bound to a carrier molecule, at least one of Z2, Z2′, Z3, Z3′, R1, R1′, R2, R2′, R3, R3′, R4, R4′, R5, R5′, R6 and R6′ is a reactive functional group, or is a linker covalently bound to a carrier molecule; and said compound comprises at least three SO3H moieties.