Conformational properties of the unnatural amino acid β-methylphenylalanine in a linear octapeptide system; correlations of 13C-NMR chemical shifts with the side-chain stereochemistry of these amino acid residues

Conformational properties of the four stereoisomers ([2S,3S], [2S,3R], [2R,3S], and [2R,3R]) of a synthetic amino acid, β-methylphenylanaline (β-MePhe), in a bioactive octapeptide sequence of CCK, H-Asp 1 -Tyr 2 -β-MePhe 3 -Gly 4 -Trp 5 -Nle 6 -Asp 7 -Phe 8 -NH 2 , have been studied by using 1 H and 13 C-2D NMR spectroscopy. β-MePhe 3 residues introduce significant perturbations to the side-chain conformations. On the basis of the rotamer populations determined by a combination of homonuclear and heteronuclear vicinal coupling constants, each of the four different stereoisomers of β-MePhe residues virtually eliminates one of the three staggered side-chain conformations, trans for (2S,3S)- and (2R,3R)-β-MePhe, gauche(+) for (2S,3R)-β-MePhe, and gauche(-) for (2R,3S)-β-MePhe, respectively