Evaluation of the vasorelaxant effect of 4, 11a 11h on rat aorta demonstrated that potency decreases with branched alkyl groups.
In agreement with the present investigation, very short peptide sequences were found to be able to reach potency also in the biological context, although with the potency decreasing for sufficiently short hydrophilic sequences.
The direct effect of MB on Tau aggregation is one of the key events in the defense against Tau-induced functional changes since MB's potency decreases with increasing β-propensity of Tau.
Further extension of an Ac-Sal unit, compound 6, increased activity to an EC50 of 2.3 μM; addition of a Lys-Sal unit, compound 1, failed to further increase potency but rather decreased potency slightly.
Based on the results, the loss in potency decreases with the number of cysteine substitutions in the order WT > 2Cys > 3Cys > 5Cys.
For instance, acylation of compounds at the N-3 position of the 2,3-benzodiazepine ring for the "M" site increases potency, but decreases the potency for those that bind to the "O" site with the same acylating group 28, 29.
Finally, the single mutation of residue 267 from phenylalanine to valine (F267 V) had a more moderate effect with only a 2-fold loss in decoquinate potency while decreasing atovaquone potency by 20-fold.
