Functionalized cyanine dyes (PEG)

摘要

The invention provides a novel class of cyanine dyes that are functionalized with a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates.

主权项

1. A compound of formula:wherein
Q is: Rm is a member selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; n is an integer selected from 1, 2, 3, 4 and 5; Rc, and Rd are independently selected from alkyl and heteroalkyl, substituted with a member selected from sulfonic acid, carboxylic acid, phosphonic acid, and phosphoric acid; each Ra and each Re, is independently selected from C(O)R9, OR12, NR12 R13, CR12C(O)R13, NR12C(O)2R13, SO3H, and C(O)NR12R13, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, and a ring structure formed by joining a member selected from two Re moieties together with the atoms to which they are attached, two Re moieties together with the atoms to which they are attached, and a combination thereof, to form said ring structure, which is a member selected from a substituted or unsubstituted aryl and a substituted or unsubstituted heteroaryl, said ring substituted with at least one SO3H, wherein
R9 is a member selected from OR10, and NH(CH2)tOR11wherein
R10 is a member selected from H and substituted or unsubstituted alkyl;t is selected from the integers from 1 to 12;R11 is a member selected from H, and wherein
u is selected from the integers from 1 to 8; andY is a naturally occurring nucleobase; andR12 and R13 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; a and e are integers independently selected from 0, 1, 2, 3 and 4; Rf, Rg, Rh, and Ri are independently selected from unsubstituted alkyl, alkylsulfonic acid, and wherein
s is selected from the integers from 1 to 12; andR9a is a member selected from OH, and
—NH(CH2)tt—O—R10a wherein
tt is selected from the integers from 1 to 12; andR10a is a member selected from H, a moiety comprising poly(ethylene glycol), and wherein
Y is a naturally occurring nucleobase; andu is selected from the integers from 1 to 8; and wherein
at least one of Ra, Re, Rf, Rg, Rh and Ri comprises a poly(ethylene glycol) moiety, and when at least one of Ra and Re comprises a poly(ethylene glycol) moiety, said at least one of Ra and Re is: wherein
b and d are integers independently selected from 0 to 18; andn is an integer from 2 to 10,000.