| Abstract
| - The 2-methylglutamic acid (2M) analogue was generallyinactive in electrophysiological experiments andhad generally worse functional activity. The low functionalactivity obtained with 2M would not bedetermined by only α substitution or C methylation, since theextensive biological studies of α,α‘-dialkylcyclic analogues of glutamic acid containing a cyclohexane and acyclopentane ring or β- or γ-methylatedglutamic acid analogues with linear flexible systems have indicatedinteresting properties. A conformationalanalysis by 1H and 13C NMR spectroscopy andmolecular modeling of 2M was undertaken inaqueoussolution to identify the preferred solution conformations and tounderstand whether its different biologicalactivities would be due to structural differences. The preferredconformation of the 2M molecule is thesterically favored one Ca, corresponding to a large “W” between themethyl and the carboxylate groupsmixed with Aa showing a large zig−zag alkylamine chain ending in acarboxylate group, or Ba, correspondingto a large “W” between the amino and the carboxylategroups.
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