抄録
To investigate the chemical conformations and functions of the -Phe-Phe-Val- or -Phe-Phe- sequences contained in the Alzheimer's disease related β-amyloid peptide, a series of mini parallel double-stranded peptides conjugated with two peptide residues to one spacer were designed and prepared. The structure of the compounds was elucidated by circular dichroism (CD) spectrum and NMR two dimensional (2D) nuclear Overhauser enhancement and exchange spectroscopy (NOESY) measurments. The structure of 1, 2-ethano-bis(L-Phe-L-Phe-L-Leu), 1, 12-dodecano-bis(L-Phe-L-Phe-L-Leu), 1, 12-dodecano-bis(L-Phe-L-Phe-L-Val), and 1, 12-dodecano (D-Phe-D-Phe-D-Leu) conjugated with L-Leu and L-Val residues show a β-turn-like nucleation. The dihedral angles (θ=+75°, +180°, ω=+90°, φ=-87°, ψ=+180°) obtained from experimental coupling constant (J) data, etc. support that 1, 12-dodecano-bis(L-Phe-L-Phe) adopts β-turn mimic nucleation. The 1, 12-dodecano-bis(L-Leu-L-Leu-L-Phe), 1, 12-dodecano-bis(L-Ile-L-Phe-L-Leu), and 1, 12-dodecano-bis(L-Phe-L-Val-L-Leu), etc. adopt most probably a random structure by CD studies.It was found by titration spectrum that an inclusion complex of 1 : 1 ratio (association constant;Ka=1.0×104M-1) is formed between 1, 12-dodecano-bis(L-Phe-L-Phe-L-Leu) and azobenzene (guest, [L0]=1.758×10-5M-1). Moreover, the stability of the complexes was increased in order of 1, 12-dodecano-bis(L-Phe-L-Phe-L-Leu)·azobenzene>1, 12-dodecano-bis(L-Phe-L-Phe-L-Val)·azobenzene>1, 12-dodecano-bis(L-Phe-L-Val-L-Leu)·azobenzene. The data show that X-Phe-L-Phe-L-spacer(S)-L-Phe-L-Phe-X (X=amino acids;S=1, 2-ethano- and 1, 12-dodecano-) plays an important role as a binding site of the artificial receptor. The hydrophobic interaction of the four Phes in the two strands is a very interesting issue in the physiological action of proteins as well as the conformation of the backbone of X-L-Phe-L-Phe-spacer(S)-L-Phe-L-Phe-X.
