A helical chain being the most common secondary structure in biopolymers prefers one-handed (left-or right-handed) screw sense, when chiral moieties are incorporated into the main or side chain through the covalent bond. We here report that an achiral helical peptide prefers the one-handed helical screw sense by noncovalent interaction of its N-terminal amino group with a chiral carboxylic acid. Little is known about such phenomena in peptide systems typical of biopolymers, although it has been reported that synthetic helical polymers bearing carboxyl or amino groups in the repeating units induce the one-handed screw sense by addition of chiral small amines or acids to interact on their polymer side or main chains. 1 In our system, the acid-base interaction occurring in the N-terminal position of the peptide chain will lead to the predominance of one-handed screw sense of the entire peptide chain, namely through domino effect. For our purpose, the following N-deprotected nonapeptide 1 consisting of nonprotein amino acids [R-aminoisobutyric acid (Aib) and R, -dehydrophenylalanine (∆ Z Phe)] was synthesized. 2 Peptide 1 can be expected to generate two "enantiomeric" (leftand right-handed) helices, since Aib and ∆ Z Phe residues are achiral ones and strong inducers for forming a 3 10 -helix. 3 Actually, a helical conformation was evidenced by 1 H NMR spectroscopy on peptide 1 in CDCl 3 . In the NOESY experiment, marked crosspeaks were observed for the N i H-N i+1 H resonances in the segment of Aib(3) to Aib(9), 2 indicating that peptide 1 forms a 3 10 -or R-helix. 4 The solvent dependence on amide NH chemical shifts in CDCl 3 /(CD 3 ) 2 SO mixtures revealed that six NH resonances of ∆ Z Phe(4) to Aib(9) residues are shielded from solvent due to intramolecular hydrogen bonding, 2 of which the pattern corresponds to a 3 10 -helix. The helical conformation was also supported by the amide I absorption bands of its FT-IR spectrum in chloroform: 1660 and 1627 cm -1 , which can be assigned to saturated amino acid and ∆ Z Phe residues in a helical segment, respectively. 5 Furthermore, energy minimization of peptide 1 by the semiempirical molecular orbital method 6 gave a 3 10 -helical conformation ( Figure 1) characterized by 〈φ〉 ) (41.1°, 〈ψ〉 ) (37.6°, and 〈ω〉 ) 180.0°for average values of ∆ Z Phe(2) to ∆ ZPhe(8) residues, and the main-chain energy contour map was severely restricted into right-and left-handed helical regions (φ ) (60 to (40°, ψ ) (60 to (30°). 2 Therefore, peptide 1 having a strong helix-forming tendency forms a 3 10 -helical conformation in chloroform. 7 Peptide 1 could not show any CD signals due to the absence of chiral residues, thus taking both left-and right-handed helices with the same content in an equilibrium state (Figure 2, dotted line). However, intense split CD signals were induced around 282 nm assignable to ∆ Z Phe residues by the addition of enantiomerically pure Boc-L-Pro-OH (Boc ) t-butoxycarbonyl), as shown in Figure 2. The mirror image was obtained by the addition of Boc-D-Pro-OH, th...

Recently, a novel chiral intermolecular interaction was found in an N-deprotected achiral nonapeptide that undergoes the predominance of one-handed screw sense through the addition of chiral small carboxylic acid (Inai, Y.; Tagawa, K.; Takasu, A.; Hirabayashi, T.; Oshikawa, T.; Yamashita, M. J. Am. Chem. Soc. 2000, 122, 11731). We here clarify to what extent such noncovalent chiral domino effect affects the helical screw sense of an N-deprotected chiral peptide. Two chiral peptides consisting of C-terminal L-Leu (1) or L-Leu(2) (2) and the preceding achiral helical octapeptide segment were employed. NMR and IR spectroscopy, and energy calculation indicated that both peptides adopt a helical conformation in chloroform. Peptide 1 showed a small excess of a left-handed screw sense for the achiral helical octapeptide, but peptide 2 strongly preferred a right-handed screw sense. The addition of chiral Boc amino acid to a chloroform solution of peptide 1, depending on its chirality, underwent a unique helix-to-helix transition or led to remarkable stabilization of the original left-handed screw sense. Peptide 2 retained the original right-handed screw sense on addition of chiral Boc-amino acid, but its helical stability changed to some extent depending on its added chirality. Therefore, the importance of noncovalent domino effect for controlling the helical screw sense or helical stability of a chiral peptide has been demonstrated here for the first time. In addition, we here have presented a unique system that both N-terminal noncovalent and C-terminal covalent domino effects operate simultaneously on the helical screw sense of a single achiral segment and have compared both powers for inducing the screw sense bias.

To understand the terminal effect of chiral residue for determining a helical screw sense, we adopted five kinds of peptides I-V containing N-and/or C-terminal chiral Leu residue(s):

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