ABSTRACT:Sequential pcptidcs containing Z-dehydrophenylalanine (,1 zPhc) residues, Boc-(L-Lcu-Ll zPhc)"-L-Leu-OMe (n = 2-6), were synthesized, and their conformations in solution were investigated using 1 H NMR and CD spectroscopy. Tridecapcptide (n=6) was shown to adopt a helical conformation in CDCI 3 by observation of successive N,H<-->N;+ 1 H nuclear Overhauser effects. Solvent accessibility ofNH resonances for peptide n=6 in CDCI 3 indicated that all the NH groups except those belonging to the N-terminal Leu-,1zPhe moiety participate in intramolecular hydrogen bonding. Similar accessibility was observed for pcptidcs n =2-5. Thus, pep tides 11 =2-6 in CDCI 3 show a (i + 3)-->i intramolecular hydrogen bonding pattern characteristic of a 31 0 -helix. CD spectra of peptides 11 = 3 6 in chloroform showed exciton couplets around 280 nm with a negative peak at longer wavelengths, corresponding to a right-handed helical sense. Ll zPhe residue was shown to be effective to design a 3 1 0 -hclical-typc backbone using sequential pep tides of (X-Ll zPhe) unit.

ABSTRACT:The present paper describes chain-length effects on helix-forming tendency in sequential peptides containing Z-deh ydrophenylalanine (8 2 Phe) residues, i.e., (X-8 2 Phe ) .. For sequential peptides Boc-( L-Leu-8 2 Phe ln-L-Leu-0 Me ( n = 2-6) that take 3 10 -helical conformation in CHC1 3 , solvent dependence on their helical structures was investigated by CD spectroscopy. CD patterns corresponding to a right-handed helix were observed for peptides n = 3-6 in CHC1 3 , tetrahydrofuran, acetonitrile, methanol, and trimethyl phosphate. Such helical structures became less stable in dimethyl sulfoxide and trifluoroethanol. Conformational energy calculation was carried out for acetyl-(L-Ala-8zPhe)"-NHCH 3 (n= 1-12). Peptides above n=2 were predicted to form helical structures preferentially. In addition, rigidity of the helical structure containing 8zPhe residues was found to be somewhat lower than that containing a-aminoisobutyric acid residue with strong helix-forming tendency. This can be ascribed to the conformational properties inherent in 8zPhe residue that induces not only helical backbones, but {J-turn backbones. The a,/J-dehydroamino acid residue has been found naturally in many peptides having biological activity and in some proteins. 1 -5 This type of residue shows inherent conformational properties due to structural features, e.g., plarnarity of ca = CP double bond and trigonal geometry of a-carbon atom. As for Z-o:,/J-dehydrophenylalanine the introduction of two or three residues into a peptide chain leads to helical structures. 6 -16 -NH-C-C0- 11