Four of the synthesized compounds, possessing analogous substitution pattern, were found able to inhibit at low micromolar concentrations endothelial cell proliferation, migration and differentiation, constitutively or in response to Vascular Endothelial Growth Factor (VEGF) and to attenuate VEGF-induced phosphorylation of VEGF receptor-2 and downstream kinases AKT and ERK1/2.
Finally, the analogous substitution to T790M in BCR-ABL, T315I, is responsible for acquired resistance to ABL inhibitors in chronic myelogenous leukemia (CML) but has also been detected in CML patients before treatment [13].
Furthermore, when the analogous substitution is made in the yeast protein, yMLH1-G64E, this protein does not sustain MMR fully and is as compromised as yMLH1-G64R.
The analogous substitution in the D-loop of the Smc1 ATPase active site, smc3-D1161E, nonlynly fails to act as a cohesion activator but also is unable to support viability, fails to load cohesin to DNA, and cannot generate cohesion.
This result contrasts with a previous report in which it was demonstrated that the analogous substitution in amFP486 results in a protein that is not blue-shifted relative to avGFP-derived CFP [ 23].
An analogous substitution is made for particular observables that are used with the Reporter property: instead of displaying 'protein/peptide modification: abnormal' where the Reporter is carboxypeptidase Y, 'carboxypeptidase Y (Prc1p) modification: abnormal' is displayed, giving an immediate indication that the phenotype involves the vacuolar protein sorting pathway.
Interestingly, the analogous tyrosine substitutions on AAV5 and AAV8 capsids did not improve the efficacy of these serotypes.
In contrast, analogous meta-substitution for the 6-APTs increases H1 affinity up to 100-fold.
The analogous R150H substitution of the DRY motif in zebrafish sphingosine-1 phosphate receptor 2 (S1producesuces a mutation, miles apart m 93) (mil(m93)), that not only disrupts signaling but also impairs heart field migration.
An analogous E17K substitution in AKT3 has also been found in melanomas (Davies et al, 2008).
