Recombinant mouse antibody (DC8E8) is capable of binding to Tau. This antibody could neutralize its target.
Figure 1 Monoclonal antibody DC8E8 inhibits pathological tau–tau interaction.
Inhibition of pathological tau–tau interaction by DC8E8. The amount of oligomerised tau (297-391/4R) was measured by thioflavin T fluorescence in the absence and in the presence of the monoclonal antibody (mAb) DC8E8 at the time points 1, 4 and 20 hours. Inhibitory activity of DC8E8 was statistically significant for the indicated time points
when analysed using a nonparametric t-test (P < 0.0001).
Kontsekova, E., Zilka, N., Kovacech, B., Skrabana, R., & Novak, M. (2014). Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer’s disease. Alzheimer's research & therapy, 6(4), 45.
Figure 2 Monoclonal antibody DC8E9 inhibits pathological tau–tau interaction.
Analysis of the inhibitory potential of DC8E8 showing prevention of the formation of tau dimers, trimers and oligomers by mis-disordered truncated tau by immunoblotting using horseradish peroxidase–conjugated mAb DC25. The positions of the molecular weight markers are indicated on the right.
Kontsekova, E., Zilka, N., Kovacech, B., Skrabana, R., & Novak, M. (2014). Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer’s disease. Alzheimer's research & therapy, 6(4), 45.
Figure 3 DC8E8 significantly reduces the number of neurofibrillary tangles in transgenic mice.
Transgenic mice were treated with mock antibody DC51(A) and(D) and with DC8E8(B) and(E). Neurofibrillary tangles (NFTs) were visualised with AT8 staining (A) and(B) and with pS214 antibody(D) and(E). Transgenic mice treated with therapeutic antibody DC8E8 showed significantly less tau pathology than mice treated with mock antibody DC51(C) and(F). * - P < 0.05; *** - P < 0.001; boxes represent 75 percentiles, middle bars represent medians and outer horizontal bars represents data range.
Kontsekova, E., Zilka, N., Kovacech, B., Skrabana, R., & Novak, M. (2014). Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer’s disease. Alzheimer's research & therapy, 6(4), 45.
Figure 4 DC8E8 discriminates between pathological and physiological‘healthy’ tau.
(A)Affinity comparison of DC8E8–four-repeat tau protein complex formation. The monoclonal antibody DC8E8 exhibits preferential affinity to the mis-disordered truncated tau 151-391/4R. Surface plasmon resonance (SPR) revealed that mis-disordered truncated tau protein is recognised by DC8E8 nearly seven times stronger than the full-length tau protein isoform. Extrapolation of kinetic SPR sensorgrams of DC8E8 interaction with mis-disordered truncated(B) and full-length (C) four-repeat tau proteins revealed that mis-disordered truncated tau is recognised by DC8E8 with kon= 2.9 × 106 M−1s−1 and koff= 0.04 s−1, whereas full-length tau exhibits kon= 4.4 × 105M−1s−1 and koff= 0.04 s−1. (D) DC8E8 affinity comparison of three-repeat truncated tau and its full-length counterpart. Similarly to the four-repeat tau, extrapolation of kinetic SPR sensorgrams of DC8E8 interaction with truncated (E) and full-length(F) three-repeat tau proteins revealed that truncated tau is recognised by DC8E8 withkon=1.5×105M−1s−1 and koff=0.08s−1, whereas full-length tau exhibitskon=2.8×104M−1s−1and koff=0.4s−1. These results show that three-repeat mis-disordered truncated tau protein is recognised by DC8E8 with 25 times higher affinity than full-length three-repeat tau protein. Black curves represent experimental data, and red curves were fitted by evaluation software for kinetic parameter calculations.
Kontsekova, E., Zilka, N., Kovacech, B., Skrabana, R., & Novak, M. (2014). Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer’s disease. Alzheimer's research & therapy, 6(4), 45.
Figure 5 The flexibility of the binding site allows DC8E8 to adapt to four homologous, albeit not identical, structural determinants in the tau microtubule-binding repeats.
Two independently refined X-ray structures of DC8E8 antigen-binding fragment (A) and(B) (stereoview) show the flexibility of the antigen-binding site. The surface of the antibody is shown in grey. The backbones of complementarity determining regions (CDRs) are represented as tubes, with the diameter and colour reflecting their averaged atomic displacement parameters, that is, flexibility. The flexibility is expressed as a colour scale ranging from blue to red, corresponding to B-factors 30 to 150 Å 2. The CDRs L1 and H3 exhibit higher B-factors than the remaining parts of the model. The pronounced flexibility of these CDRs is essential to allowing DC8E8 to bind each of four slightly different epitopes within the microtubule-binding repeats (MTBRs).(C) Superposition of both independently refined DC8E8 molecules shows that the core of the binding pockets is invariant (molecule A shown as grey solid, molecule B as blue mesh). The CDR loops (italic letters) create a 7- to 9-Å-deep pocket with surface dimensions 18 × 14 Å (red axes). The shape of this pocket necessitates that the minimal DC8E8 epitope HXPGGG adopts a fold protruding into this space to bind in the DC8E8 combining site.
Kontsekova, E., Zilka, N., Kovacech, B., Skrabana, R., & Novak, M. (2014). Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer’s disease. Alzheimer's research & therapy, 6(4), 45.
This is a product of Creative Biolabs' Hi-Affi™ recombinant antibody portfolio, which has several benefits including:
• Increased sensitivity
• Confirmed specificity
• High repeatability
• Excellent batch-to-batch consistency
• Sustainable supply
• Animal-free production
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CAT | Product Name | Application | Type |
---|---|---|---|
PABL-340 | Mouse Anti-MAPT Recombinant Antibody (clone AT8) | ELISA, FuncS | Mouse IgG |
HPAB-0042-WJ | Human Anti-MAPT Recombinant Antibody (HPAB-0042-WJ) | ELISA, WB | Humanized IgG4 |
MRO-2209-CN | Rabbit Anti-MAPT Polyclonal Antibody (MRO-2209-CN) | WB, IF, IHC | Rabbit IgG |
HPAB-AP145-YC | Human Anti-MAPT Recombinant Antibody (HPAB-AP145-YC) | ELISA | Human IgG1 |
HPAB-N0170-YC | Human Anti-MAPT Recombinant Antibody (HPAB-N0170-YC) | ELISA, Inhib | Humanized IgG |
CAT | Product Name | Application | Type |
---|---|---|---|
PSBL-305 | Chicken Anti-MAPT Recombinant Antibody; scFv Fragment | WB, ELISA, FuncS | Chicken scFv |
PSBL-340 | Mouse Anti-MAPT Recombinant Antibody (clone AT8); scFv Fragment | ELISA, FuncS | Mouse scFv |
HPAB-1001WJ-S(P) | Human Anti-MAPT Recombinant Antibody; scFv Fragment (HPAB-1001WJ-S(P)) | ELISA, WB | Humanized scFv |
HPAB-1002WJ-S(P) | Human Anti-MAPT Recombinant Antibody; scFv Fragment (HPAB-1002WJ-S(P)) | ELISA, WB | Humanized scFv |
HPAB-1003WJ-S(P) | Human Anti-MAPT Recombinant Antibody; scFv Fragment (HPAB-1003WJ-S(P)) | ELISA, WB | Humanized scFv |
CAT | Product Name | Application | Type |
---|---|---|---|
PFBL-305 | Chicken Anti-MAPT Recombinant Antibody; Fab Fragment | WB, ELISA, FuncS | Chicken Fab |
PFBL-705 | Mouse Anti-MAPT Recombinant Antibody (clone DC8E8); Fab Fragment | WB, IF, FuncS | Mouse Fab |
PFBL-706 | Rabbit Anti-MAPT Recombinant Antibody (clone RB86); Fab Fragment | WB, IF, FuncS | Rabbit Fab |
NS-090CN-F(E) | Mouse Anti-MAPT Recombinant Antibody; Fab Fragment (NS-090CN-F(E)) | WB, ELISA, IHC, IP | Mouse Fab |
HPAB-0042-WJ-F(E) | Human Anti-MAPT Recombinant Antibody; Fab Fragment (HPAB-0042-WJ-F(E)) | ELISA, WB | Humanized Fab |
CAT | Product Name | Application | Type |
---|---|---|---|
BRD-0733MZ | Chicken Anti-TAU Polyclonal IgY | ICC/IF, IHC, WB | Chicken antibody |
CAT | Product Name | Application | Type |
---|---|---|---|
PABX-174 | Recombinant Mouse Anti-Tau5 Antibody | WB, ELISA, Neut, FuncS | IgG |
PABX-174-S (P) | Recombinant Mouse Anti-Tau5 Antibody scFv Fragment | WB, ELISA, Neut, FuncS | scFv |
PABX-174-F (E) | Recombinant Mouse Anti-Tau5 Antibody Fab Fragment | WB, ELISA, Neut, FuncS | Fab |
CAT | Product Name | Application | Type |
---|---|---|---|
MOR-2164 | Hi-Affi™ Recombinant Rabbit Anti-MAPT Monoclonal Antibody (DS2164AB) | IHC-P | IgG |
MOR-4513 | Hi-Affi™ Recombinant Rabbit Anti-MAPT Monoclonal Antibody (TH21DS) | WB, IHC-P, FC | IgG |
MOR-4714 | Hi-Affi™ Recombinant Rabbit Anti-MAPT Monoclonal Antibody (TH228DS) | WB, IF, ICC, IHC-P, FC | IgG |
MOR-4715 | Hi-Affi™ Recombinant Rabbit Anti-MAPT Monoclonal Antibody (TH229DS) | WB, IF, ICC, IHC-P | IgG |
CAT | Product Name | Application | Type |
---|---|---|---|
NS-090CN | Mouse Anti-MAPT Recombinant Antibody (NS-090CN) | WB, ELISA, IHC, IP, SPR, FuncS | Mouse IgG2b |
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