Pre-treatment with ESL inhibited the TPA-stimulated NF-κB binding activity, but not the AP-1 binding activity, suggesting that ESL specifically blocks NF-κB activation in MCF-7 cells.
Similarly, the COX-2 selective NSAID NS-398 induced an increase in NF-κB DNA binding activity but not in NF-κB-reporter gene expression in colon cancer cells while indomethacin, a drug closely related to sulindac, was reported to induce gastropathy through activation of NF-κB in gastric microvascular endothelial cells [ 51, 52].
In this model we observed a dependency of TDP-43-mediated neurotoxicity on RNA-binding activity, but not mislocalization, truncation, or missense mutations, therefore accurately mirroring the results obtained by same-level TDP-43 expression in Drosophila.
Lastly, compounds containing tin (e.g., tributyltin) and mercury (e.g., phenylmercuric acetate) broadly disrupted GPCR ligand-binding activities but not kinase or phosphatase activities.
In sum, these data show that MIEF1 reduces Drp1's GTP-binding activity, but does not affect oligomerization or phosphorylation of Drp1, and conversely, the phosphorylation status of Drp1-Ser637 is not critical for its interaction with MIEF1.
Thus, conversion of a drug to a macromolecular form may not only sustain its binding activity but may also lead in a higher selectivity.
ERBB2, the main player of the ERBB network, does not show any ligand binding activity, but has high dimerization affinity [ 5, 6].
In addition, biological activity assays of such glycoengineered mAbs showed that their antigen binding activity was not altered but significantly enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) effect [ 70, 71].
Hence, it seems that HN mutations induce a defect in both functions simultaneously and that generation of an HN protein that possess functional receptor-binding activity but lacks NA activity should not be possible.
Antigen binding activity was not compromised by altered glycosylation or Fc mutagenesis, whereas Fc binding to CD16a was significantly enhanced in the order: non-core fucosylated/Fc-mutated double-engineered ≫ Fc-mutated ≥ non-core-fucosylated > wild-type IgG1-Fc.
Uninfected cells did not show NF-κB or AP-1 DNA binding activity (data not shown).
