C-13 relaxation studies on side-chain methyl groups in proteins typically involve measurements on (CHD2)-C-13 isotopomers, where the C-13 relaxation mechanism is particularly straightforward in the presence of a single proton. While such isotopomers can be obtained in proteins overexpressed in bacteria by use of C-13 enriched and fractionally deuterated media, invariably all possible H-2 isotopomers are obtained. This results in a loss of both resolution and sensitivity, which becomes particularly severe for larger proteins. We describe an approach that overcomes this problem by chemical synthesis of amino acids containing a pure (CHD2)-C-13 isotopomer. We illustrate the benefits of this approach in C-13 side-chain relaxation measurements on the mouse major urinary protein selectively enriched with [gamma(1),gamma(2)-C-13(2),alpha,beta,gamma(1),gamma(1),gamma(2),gamma(2)-H-2(6)] valine. Relaxation measurements in the absence and presence of pyrazine-derived ligands suggest that valine side-chain dynamics do not contribute significantly to binding entropy.