Cell-penetrating markers of apoptosis

摘要

Provided herein are compounds useful for selectively labeling an apoptotic cell, and methods and assays using such compounds for the detection of an apoptotic cell in vivo or in a biological sample obtained from a subject.

主权项

1. An assay for detecting apoptosis in a biological sample comprising a cell, the method comprising:
analyzing a biological sample comprising a cell for the presence of a fluorescent cell, wherein the biological sample was contacted with a fluorescent compound of formula (I) wherein
R1 is hydrogen, SO3−, OH, OR5; COOH, COOR5, NH2, or N(RB)2;X1 is OH, NH2, N(R7R8); CF3, CN, C(O)RB, CO2RB, C(O)N(RB)2, ORB, N(RB)2, N═C═S, NHC(O)RB, NHC(O)ORB, NHC(S)RB, NHC(S)N(RB)2, NHSO2RB, NHSO2N(RB)2, NO2, N2—RB, SORB, SO2RB, SO3RB, OP(O)(OH)2, optionally substituted linear or branched C1-C10 alkyl, optionally substituted linear or branched C2-C10 alkenyl, optionally substituted linear or branched C2-C10 alkynyl, optionally substituted cyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;X2 is O, NH2, or N(R7R8);each R2 is independently hydrogen, halogen, CF3, alkyl, OH, or taken together with either X1 or X2 forms optionally substituted carbocyclic, optionally substituted heterocyclic, optionally substituted aryl, or optionally substituted heteroaryl;R3 is C(O)R4, or N(H)R4;R4 is hydrogen, cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; RB; OH; ORB; —NH(RB); —N(RB)2; —C(═O)NH(RB); —C(═O)N(RB)2; —C(═S)NH(RB); —C(═S)N(RB)2;each RB is independently hydrogen; halogen; a protecting group; aliphatic; heteroaliphatic; acyl; aryl moiety; heteroaryl; hydroxyl; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; heteroarylthioxy; or alkylhalo;R5 is a protecting group; aliphatic; heteroaliphatic; acyl; aryl moiety; or heteroaryl; andeach R7 and R8 is independently hydrogen, or alkyl;R is hydrogen, C1-6alkyl, or COOR9;R9 is hydrogen, or C1-4alkyl, wherein the compound formula (I) selectively labels apoptotic cells and does not level non-apoptotic cells, and wherein the presence of a fluorescent cells permits detection of apoptotic in the biological sample.