A comparison of solution conformations of scyliorhinin I and its analogue with N-methyl-L-phenylalanine in position 7

Conformational studies on scyliorhinin I (ScyI), a member of tachykinin fam ily and its analogue with N-methyl-L-phenylalanine in position 7 in DMSO-d( 6) were performed using a combination of the two-dimensional NMR technique and theoretical conformational analysis. Their solution structures are char acterized by families consisting of 7 and 8 conformers, respectively, with statistical weights higher than 2%. The 3D structure of ScyI is rather flex ible, whereas the presence of a local constraint (MePhe) in position 7 sign ificantly rigidifies the whole molecule. The comparison of conformers with the greatest statistical weights obtained for both peptides revealed the si milarities in the fragment 1-7, whereas C-terminal segments are quite diffe rent (RMSD = 2.26 Angstrom). We postulate that this can be connected with t he differences of the pharmacological profiles of both peptides (ScyI full agonist of both Ngl and NK2 tachykinin receptors; [MePhe(7)]ScyI is practic ally inactive).