External Chirality-Triggered Helicity Control Promoted by Introducing alpha beta-Ala Residue into the N-Terminus of Chiral Peptides

摘要

The noncovalent chiral domino effect(NCDE),defined as chiral interaction upon an N-terminus of a 3_10-helical peptide,will provide a unique method for structural control of a peptide helix through the use of external chirality.On the other hand,the NCDE has not been considered to be effective for the helicity control of peptides strongly favoring a one-handed screw sense.We here aim to promote the NCDE on peptide helicity using two types of nonapeptides:H-beta-Ala-DELTA~ZPhe-Aib-DELTA~ZPhe-X~*-(DELTA~ZPhe-Aib)_2-OCH_3 [DELTA~Z-Phe = alpha,beta-didehydrophenylalanine,Aib = alpha-aminoisobutyric acid],where X~* as the single chirality is L-leucine(1)or L-phenylalanine(2).NMR,IR,and CD spectroscopy as well as energy calculation revealed that both peptides alone form a right-handed 3_10-helix.The original CD amplitudes or signs in chloroform,irrespective of a strong screw-sense preference in the central chirality,responded sensitively to external chiral information.Namely added Boc-L-amino acid stabilized the original right-handed helix,while the corresponding D-isomer destabilized it or transformed it into a left-handed helix.These peptides were also shown to bind more favorably to an L-isomer from the racemate.Although similar helicity control was observed for analogous nonapeptides bearing an N-terminal Aib residue(Inai,Y.;et al.Biomacromolecules 2003,4,122),the present findings demonstrate that the N-terminal replacement by the beta-Ala residue significantly improves the previous NCDE to achieve more effective control of helicity.Semiempirical molecular orbital calculations on complexation of peptide 2 with BOC-(L or D)-Pro-OH reasonably explained the unique conformational change induced by external chirality.