Acetaldehyde--enkephalins: structure proof and some conformational deductions from one- and two-dimensional proton...

The structure of the adduct formed by reaction of acetaldehyde and Met5-enkephalin has been determined by analysis of 400-MHz proton spectra: two-dimensional J spectroscopy was used to resolve and measure virtually all the overlapping resonances, and decoupling difference spectroscopy was used to assign the resonances. Suitable manipulation of the two-dimensional data allowed analysis of alpha-CH resonances which were completely buried under a water signal and of amide NH resonances which overlapped in both dimensions. The adduct was shown to be a mixture of two diastereoisomers, each containing a 2-methylimidazolidin-4-one ring formed by condensation of an acetaldehyde molecule with the N-terminal amino group and Gly2 amide nitrogen. Analysis of the NMR data suggests that the folded conformation characteristic of native enkephalins in dimethyl-d6 sulfoxide is not important in these derivatives.