Chirality transmission in macromolecular domains

Abstract

Chiral communications exist in secondary structures of foldamers and copolymers via a network of noncovalent interactions within effective intermolecular force (IMF) range. It is not known whether long-range chiral communication exists between macromolecular tertiary structures such as peptide coiled-coils beyond the IMF distance. Harnessing the high sensitivity of single-molecule force spectroscopy, we investigate the chiral interaction between covalently linked DNA duplexes and peptide coiled-coils by evaluating the binding of a diastereomeric pair of three DNA-peptide conjugates. We find that right-handed DNA triple helices well accommodate peptide triple coiled-coils of the same handedness, but not with the left-handed coiled-coil stereoisomers. This chiral communication is effective in a range (<4.5 nm) far beyond canonical IMF distance. Small-angle X-ray scattering and molecular dynamics simulation indicate that the interdomain linkers are tightly packed via hydrophobic interactions, which likely sustains the chirality transmission between DNA and peptide domains. Our findings establish that long-range chiral transmission occurs in tertiary macromolecular domains, explaining the presence of homochiral pairing of superhelices in proteins.

Unraveling Dynamic Helicity Inversion and Chirality Transfer through the Synthesis of Discrete Azobenzene Oligomers by an Iterative Exponential Growth Strategy

“…Two chiral azocontaining monomers (R-TBDPS-Azo-tBu and S-TBDPS-Azo-tBu) with two reactive groups, including the hydroxyl group protected by tert-butyldiphenylsilyl (TBDPS) group and the carboxyl group protected by tert-butyl ester (t-Bu) group, were pre-synthesized to provide precursors for these monodisperse oligomers (Scheme S1 and Figure 1a). The chemical structures of two monomers and their intermediates were confirmed by 1 H NMR spectroscopy (Figures S1-S3), showing e.e. values higher than 99 % (Figure S4).…”

“…[13b,18] Compared with chiral polymers containing azobenzene side-chains, there are fewer reports on the dynamic chiral assembly of polymers containing azobenzene in the backbone. This mainly due to three reasons: (1) the precise synthesis of well-defined main-chain azopolymers is relatively challenging; (2) the ordered chiral supramolecular stacking between the azobenzene structural units in the polymer backbone is difficult to occur due to the limited movement caused by the huge steric hindrance; (3) it is also difficult for the azobenzene bonds in the polymer backbone to undergo cis-trans isomerization. Furthermore, it is worth noting that the chiral assemblies obtained from main-chain azopolymers primarily arise from the axial chirality of the functional groups.…”

Stereoselective Plasmonic Interaction in Peptide‐tethered Photopolymerizable Diacetylenes Doped with Chiral Gold Nanoparticles

“…Such remarkable induced CD signature was attributed to increased π-π delocalization upon photopolymerization along with transfer of chirality from the amino acid moieties to the polydiacetylene chromophore as reported in other macromolecular systems with secondary structural domains showing long-range chiral transmission. [20] The difference in the CD signals for L-FF-PDA and D-FF-PDA could be attributed to the geometrical difference in conformation of the D-and L-peptide to facilitate larger helical transformation [21] (Figure 3B) and was corroborated with low pitch length to promote more ellipticity (Figure 2E). The linear dichroism (LD) spectra for the L-and D-FF-DA films suggested a minimum contribution of LD signal towards such supramolecular helicity (Figure S16A).…”

Robust single membrane protein tweezers

“…In this case, the close proximity to the large-area surface and/or between the consecutivelyconnected proteins of the tandem repeat can hinder membrane protein studies since the lipid bilayer mimetics such as bicelles or vesicles of ~100 nm or larger in diameter will not be properly accommodated in the narrow space 19,33 . On the other hand, single-molecule tweezers using hundreds-of-nm long molecular handles flanking a protein of interest still rely on the conventional noncovalent tethers of the dig-antidig and biotin-streptavidin [10][11][12][13][14][15]19 . The digantidig interaction is as very weak as τ off = ~1 sec at 25 pN (~0.1 sec at 50 pN) 24 , limiting the stable performance of experiments, data throughputs (tens of pulling on one molecule at most), and reliable statistical analyses.…”

“…To apply mechanical force to a target protein in magnetic or optical tweezers [4][5][6][7] , we tether two protein positions, e.g., the N-and C-termini, to solid supports of a micron-sized bead and the sample chamber surface (or another bead), respectively. Rapid noncovalent tethering has been widely used, such as the binding between digoxigenin (dig) and antidigoxigenin (antidig), 6xHis tag and Ni-NTA, and biotin and streptavidin [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] . However, the noncovalent tethers are dissociated in tens-of-pN force ranges 23,24 , restricting the utilization of the tweezer methods.…”