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Conformational Switching of a Foldamer in a Multicomponent System by pH-Filtered Selection between Competing Noncovalent Interactions.

Brioche J, Pike SJ, Tshepelevitsh S, Leito I, Morris GA, Webb SJ, Clayden J - J. Am. Chem. Soc. (2015)

Bottom Line: As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by (13)C NMR, is induced in the foldamer.Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations.As a result, the foldamer-ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a "proton-counting" molecular device capable of providing a tunable, pH-dependent conformational response to its environment.

View Article: PubMed Central - PubMed

Affiliation: †School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom.

ABSTRACT
Biomolecular systems are able to respond to their chemical environment through reversible, selective, noncovalent intermolecular interactions. Typically, these interactions induce conformational changes that initiate a signaling cascade, allowing the regulation of biochemical pathways. In this work, we describe an artificial molecular system that mimics this ability to translate selective noncovalent interactions into reversible conformational changes. An achiral but helical foldamer carrying a basic binding site interacts selectively with the most acidic member of a suite of chiral ligands. As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by (13)C NMR, is induced in the foldamer. Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations. As a result, the foldamer-ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a "proton-counting" molecular device capable of providing a tunable, pH-dependent conformational response to its environment.

No MeSH data available.


Conformationalpreference of foldamer F4 (h.e.) atdifferent concentrations of F4 in CDCl3 at296 K with a fixed ratio HA:F4: blue ●,experimental data for HA1:F4 = 1.5:1; red■, experimental data for HA4:F4 =1.2:1; and green ▲, experimental data for HA6:F4 = 1.2:1.
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fig3: Conformationalpreference of foldamer F4 (h.e.) atdifferent concentrations of F4 in CDCl3 at296 K with a fixed ratio HA:F4: blue ●,experimental data for HA1:F4 = 1.5:1; red■, experimental data for HA4:F4 =1.2:1; and green ▲, experimental data for HA6:F4 = 1.2:1.

Mentions: Conformational induction in the HA4↔F4 pair was remarkably concentration-independent: the inducedhelicalexcess was constant for [F4] ranging from 10 mM to 0.1mM (ratio HA:F fixed at 1.2:1, Figure 3). In HA6↔F4, theconformational preference was likewise almost constant down to 0.1mM. In the less strongly bound pair HA1↔F4, h.e. varied little between 5 and 10 mM, but fell markedlyat lower concentrations. These results also give a qualitative indicationof the strength of binding in the HA↔F4 pairs, with HA6↔F4 ≥ HA4↔F4 > HA1↔F4. The conformational effect of all three ligands was muchweaker in the presence of a protic solvent: for example, additionof 2% MeOH to the solution in CDCl3 induced a significantdrop in the value of Δδ for the HA4↔F4 interaction (SI Figure S56).


Conformational Switching of a Foldamer in a Multicomponent System by pH-Filtered Selection between Competing Noncovalent Interactions.

Brioche J, Pike SJ, Tshepelevitsh S, Leito I, Morris GA, Webb SJ, Clayden J - J. Am. Chem. Soc. (2015)

Conformationalpreference of foldamer F4 (h.e.) atdifferent concentrations of F4 in CDCl3 at296 K with a fixed ratio HA:F4: blue ●,experimental data for HA1:F4 = 1.5:1; red■, experimental data for HA4:F4 =1.2:1; and green ▲, experimental data for HA6:F4 = 1.2:1.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4520694&req=5

fig3: Conformationalpreference of foldamer F4 (h.e.) atdifferent concentrations of F4 in CDCl3 at296 K with a fixed ratio HA:F4: blue ●,experimental data for HA1:F4 = 1.5:1; red■, experimental data for HA4:F4 =1.2:1; and green ▲, experimental data for HA6:F4 = 1.2:1.
Mentions: Conformational induction in the HA4↔F4 pair was remarkably concentration-independent: the inducedhelicalexcess was constant for [F4] ranging from 10 mM to 0.1mM (ratio HA:F fixed at 1.2:1, Figure 3). In HA6↔F4, theconformational preference was likewise almost constant down to 0.1mM. In the less strongly bound pair HA1↔F4, h.e. varied little between 5 and 10 mM, but fell markedlyat lower concentrations. These results also give a qualitative indicationof the strength of binding in the HA↔F4 pairs, with HA6↔F4 ≥ HA4↔F4 > HA1↔F4. The conformational effect of all three ligands was muchweaker in the presence of a protic solvent: for example, additionof 2% MeOH to the solution in CDCl3 induced a significantdrop in the value of Δδ for the HA4↔F4 interaction (SI Figure S56).

Bottom Line: As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by (13)C NMR, is induced in the foldamer.Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations.As a result, the foldamer-ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a "proton-counting" molecular device capable of providing a tunable, pH-dependent conformational response to its environment.

View Article: PubMed Central - PubMed

Affiliation: †School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom.

ABSTRACT
Biomolecular systems are able to respond to their chemical environment through reversible, selective, noncovalent intermolecular interactions. Typically, these interactions induce conformational changes that initiate a signaling cascade, allowing the regulation of biochemical pathways. In this work, we describe an artificial molecular system that mimics this ability to translate selective noncovalent interactions into reversible conformational changes. An achiral but helical foldamer carrying a basic binding site interacts selectively with the most acidic member of a suite of chiral ligands. As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by (13)C NMR, is induced in the foldamer. Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations. As a result, the foldamer-ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a "proton-counting" molecular device capable of providing a tunable, pH-dependent conformational response to its environment.

No MeSH data available.