Transfer of Noncovalent Chiral Information along an Optically Inactive Helical Peptide Chain: Allosteric Control of Asymmetry of the C-Terminal Site by External Molecule that Binds to the N-Terminal Site
journal contributionposted on 20.02.2009, 00:00 by Naoki Ousaka, Yoshihito Inai
This study aims at demonstrating end-to-end transfer of noncovalent chiral information along a peptide chain. The domino-type induction of helical sense is proven by using achiral peptides 1-m of bis-chromophoric sequence with different chain lengths: H-(Aib-ΔZPhe)m-(Aib-ΔZBip)2-Aib-OCH3 [m = 2, 4, and 6; Aib = α-aminoisobutyric acid; ΔZPhe = (Z)-α,β-didehydrophenylalanine; ΔZBip = (Z)-β-(4,4′-biphenyl)-α,β-didehydroalanine]. They all showed the tendency to adopt a 310-helix. Whereas peptide 1-m originally shows no circular dichroism (CD) signals, marked CD signals were induced at around 270−320 nm based on both the β-aryl didehydroresidues by chiral Boc-proline (Boc = tert-butoxycarbonyl). The observed CD spectra were interpreted on the basis of the exciton chirality method and theoretical CD simulation of several helical conformations that were energy-minimized. The experimental and theoretical CD analysis reveals that Boc-l-proline induces the preference for a right-handed helicity in the whole chain of 1-m. Such noncovalent chiral induction was not observed in the corresponding N-terminally protected 1-m. Obviously, helicity induction in 1-m originates from the binding of Boc-proline to the N-terminal site. In the 17-mer (1-6), the information of helix sense reaches the 16th residue from the N-terminus. We have monitored precise transfer of noncovalent chiral stimulus along a helical peptide chain. The present study also proposes a primitive allosteric model of a single protein-mimicking backbone. Here chiral molecule binding the N-terminal site of 1-6 controls the chiroptical signals and helical sense of the C-terminal site about 30 Å away.