Solution conformation study of substance P methyl ester and [Nle 10 ]‐neurokinin A (4–10) by nmr spectroscopy

High‐resolution proton spectra at 500 MHz of two tachykinin peptides, substance P methyl ester (SPOMe) and [Nle 10 ]‐neurokinin A (4–10), have been obtained in dimethylsulfoxide (DMSO), and for SPOMe, also in 2, 2, 2‐trifluoroethanol (TFE)/water mixtures. Complete chemical shift assignments for these peptides were made based on two‐dimensional (2D) nmr techniques, correlated spectroscopy and total COSY. J coupling measurement and nuclear Overhauser effect spectroscopy (NOESY) were then used to determine the conformation of these peptides in the various solvents. Based on the J coupling, NOE correlations, and temperature coefficients of the NH resonances, it is concluded that these two peptides exist in DMSO at room temperature as a mixture of conformers that are primarily extended. For SPOMe in TFE/water with high TFE content, however, helical structures are found to be present, and they become quite clear at temperatures between 270 and 280 K. The variation of the 13 C chemical shifts of the C α (the secondary shift) with TFE contents corroborates this conclusion. The NOE and C α shifts show that the main helical region for SPOMe lies between 4 P and 9 G. The C‐terminus segment LMNH 2 is found to be quite flexible, which appears to be quite common for neurokinin‐1 selective peptides. © 1993 John Wiley & Sons, Inc.