反向信號(hào)傳遞現(xiàn)象正逐漸受到人們的關(guān)注。簡(jiǎn)言之?,即可溶性受體或膜表面受體與表達(dá)在細(xì)胞膜表面的相應(yīng)配體結(jié)合后?,傳遞信號(hào)至表達(dá)配體的細(xì)胞內(nèi)?,并引發(fā)相應(yīng)的生物學(xué)效應(yīng)。目前?,對(duì)于這一熱點(diǎn)的研究多集中于ＴＮＦ配體超家族成員。Adipogen提供多種TNF配體多聚蛋白，這些蛋白均具有高活性，低內(nèi)毒素的特點(diǎn)。

TNF Ligands Multimeric Proteins

Higher Activity – Lower Endotoxin

AdipoGen^? Multimeric Proteins are high activity constructs in which two trimeric TNFSF ligands are linked via the oligomeric collagen domain of ACRP30 [ACRP30headless] and therefore mimic the membrane-bound forms of the proteins.

Endogenous TNF superfamily ligands are either active as membrane- form (e.g. FasL, TRAIL, CD40L, OX40L) or are secreted and activated through oligomerization by the binding of pro-teoglycans at the surface of cells (e.g. APRIL). ? To mimic endogenous TNF ligands activity, the oligomerization of recombinant TNF ligands can be triggered: ? ??by fusing the TNF superfamily ligands, soluble form, to the collagen domain of the protein ACRP30 (which itself has no functional activity) to form a hexameric structure and therefore creating “Multimeric Proteins”, or ? ??by adding a cross-linking antibody called “TNF Ligands Enhancer” (Prod. No. AG-35B-0001).

MultimericFasL. [MegaFasL.]

FasL (human) (multimeric) (rec.)

AG-40B-0130 10 μg | 3 x 10 μg

MultimericFasL? very effectively simulates the natural membrane-assisted aggregation of FasL in vivo.

Source: ? ? ? ? ? ? ? ? ? ? ? ? ? ?HEK 293 cells.

Sequence: ? ? ? ? ? ? ? ? ? ? ??Human FasL (aa 139-281) is fused at the

? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ??N-terminus to mouse ACRP30headless

? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?? ?(aa 18-111) and a FLAG?-tag.

Specificity:? ? ? ? ? ? ? ? ? ? ? ?Binds to human and mouse Fas.

Biological Activity:? ? ? ? ? Induces apoptosis of human Jurkat

? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ??T cells at a concentration of<1ng/ml.

Endotoxin Content:? ? ? ?<0.01EU/μg purified protein (LAL test; Lonza).

LITerature references:? Two adjacent trimeric Fas ligands are required for Fas?signaling and formation of a death-inducing signaling complex: N. Holler, et al.; Mol. Cell. Biol. 23, 1428 (2003) ? A Fas agonist induces high levels of apoptosis in haematological malignancies: P. Greaney, et al.; Leuk. Res. 30, 415 (2006)

Figure: Oligomerisation of FasL (human) efficiently triggers Jurkat cell death.

Method: Jurkat cells were treated O/N with the indicated concentrations of FasL (human)?(multimeric) (rec.) (AG-40B-0130), Fc (human):FasL (human) (rec.) (AG-40B-0132), FasL (human) (rec.) (AG-40B-0001) or FasL (human) (rec.) + Enhancer (AG-44B- 0001) (2 fold-dilutions, first concentration of 1000ng/ml). Cell death was quantified using PMS/MTS. The oligomeric FasL recombinant proteins (FasL (human) (multimeric), Fc (human):FasL (human) and FasL (human) + Enhancer) kill Jurkat cells at IC₅₀?<0.2ng/ml.

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? MultiPacks for additional big savings !

? Bulk Quantities for in vivo cancer immunotherapy and vaccination studies in mice !

MultimericCD40L?

CD40L?(human) (multimeric) (rec.)

AG-40B-0010-C010 10 μg | 3 x 10 μg

??MultimericCD40L? very effectively mimics the natural?membrane-assisted aggregation of CD40L. It is the most potent alternative to activate CD40.?No enhancer is required.

??MultimericCD40L? is a potent B cell activator.

LITerature reference:?IgG subclass switch capacity is low in switched and in IgM-

only, but high in IgD+IgM+, post-germinal center (CD27+) human B cells: C. Werner-Favre, et al.; Eur. J. Immunol. 31, 243 (2001)

Bulk available for in vivo studies!

Full Panel of MultimericLigands?

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