1252803-35-2Relevant academic research and scientific papers
Glycopeptide dendrimer colchicine conjugates targeting cancer cells
Johansson, Emma M.V.,Dubois, Jo?lle,Darbre, Tamis,Reymond, Jean-Louis
supporting information; experimental part, p. 6589 - 6597 (2010/10/04)
Screening of a 65,536-member one-bead-one-compound (OBOC) combinatorial library of glycopeptide dendrimers of structure ((βGal)n +1X8X7X6X5) 2DapX4X3X2X1(β-Gal) m (βGal = β-galactosyl-thiopropionic acid, X8-1= variable amino acids, Dap = l-2,3-diaminopropionic acid, n, m = 0, or 1 if X8= Lys resp. X1= Lys) for binding of Jurkat cells to the library beads in cell culture, resynthesis and testing lead to the identification of dendrimer J1 (βGal-Gly-Arg-His-Ala)2Dap-Thr- Arg-His-Asp-CysNH2 and related analogues as delivery vehicles. Cell targeting is evidenced by FACS with fluorescein conjugates such as J1F. The colchicine conjugate J1C is cytotoxic with LD50 = 1.5 μM. The β-galactoside groups are necessary for activity, as evidenced by the absence of cell-binding and cytotoxicity in the non-galactosylated, acetylated analogue AcJ1F and AcJ1C, respectively. The pentagalactosylated dendrimer J4 βGal4(Lys-Arg-His-Leu)2Dap-Thr-Tyr-His-Lys(βGal) -Cys) selectively labels Jurkat cell as the fluorescein derivative J4F, but its colchicine conjugate J4C lacks cytotoxicity. Tubulin binding assays show that the colchicine dendrimer conjugates do not bind to tubulin, implying intracellular degradation of the dendrimers releasing the active drug.
