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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.


Related in: MedlinePlus

Conformational preferenceof foldamer F4 (h.e.) atdifferent ratios of HA:F in CDCl3 at 296 K: 8.8 < [F4] < 10.0 mM for titrationexperiment with HA1; [F4] = 10.0 mM fortitration experiments with HA4 and HA6;blue ●, experimental data for HA1; red ■,experimental data for HA4; green ▲, experimentaldata for HA6. Curve fits shown for a 1:1 binding modelusing the program DynaFit: K = 103 M–1 (blue —), K = 105 M–1 (red —); Curve fit shown for a 2:1binding model using the program DynaFit: K = 107 M–1 and K′ = 104 M–1 (green —).
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fig2: Conformational preferenceof foldamer F4 (h.e.) atdifferent ratios of HA:F in CDCl3 at 296 K: 8.8 < [F4] < 10.0 mM for titrationexperiment with HA1; [F4] = 10.0 mM fortitration experiments with HA4 and HA6;blue ●, experimental data for HA1; red ■,experimental data for HA4; green ▲, experimentaldata for HA6. Curve fits shown for a 1:1 binding modelusing the program DynaFit: K = 103 M–1 (blue —), K = 105 M–1 (red —); Curve fit shown for a 2:1binding model using the program DynaFit: K = 107 M–1 and K′ = 104 M–1 (green —).

Mentions: Havingidentified the 2-pyridylacetamide motif B4 as a strongcandidate in the search for a versatile and effective binding sitefor the development of a multicomponent signaling system, we nextstudied the stability of the ligand-foldamer pairs HA1↔F4, HA4↔F4,and HA6↔F4 with respect to excessligand and concentration. Varying the ratio HA1:F4 (Figure 2) gave a maximum inducedhelical excess of 55% for a ratio HA1:F4 >3:1. A similar trend was observed for HA4↔F4 with a maximum value around 59% h.e. for a ratio HA4:F4 >1:1. In the case of HA6↔F4, the maximum conformational induction (around6% h.e.)was obtained with a ratio HA6:F4 = 1.2:1.In this case only, the Δδ value dropped in the presenceof an excess of HA6, falling to 0 in the presence of2.7 equiv of the ligand.


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)

Conformational preferenceof foldamer F4 (h.e.) atdifferent ratios of HA:F in CDCl3 at 296 K: 8.8 < [F4] < 10.0 mM for titrationexperiment with HA1; [F4] = 10.0 mM fortitration experiments with HA4 and HA6;blue ●, experimental data for HA1; red ■,experimental data for HA4; green ▲, experimentaldata for HA6. Curve fits shown for a 1:1 binding modelusing the program DynaFit: K = 103 M–1 (blue —), K = 105 M–1 (red —); Curve fit shown for a 2:1binding model using the program DynaFit: K = 107 M–1 and K′ = 104 M–1 (green —).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4520694&req=5

fig2: Conformational preferenceof foldamer F4 (h.e.) atdifferent ratios of HA:F in CDCl3 at 296 K: 8.8 < [F4] < 10.0 mM for titrationexperiment with HA1; [F4] = 10.0 mM fortitration experiments with HA4 and HA6;blue ●, experimental data for HA1; red ■,experimental data for HA4; green ▲, experimentaldata for HA6. Curve fits shown for a 1:1 binding modelusing the program DynaFit: K = 103 M–1 (blue —), K = 105 M–1 (red —); Curve fit shown for a 2:1binding model using the program DynaFit: K = 107 M–1 and K′ = 104 M–1 (green —).
Mentions: Havingidentified the 2-pyridylacetamide motif B4 as a strongcandidate in the search for a versatile and effective binding sitefor the development of a multicomponent signaling system, we nextstudied the stability of the ligand-foldamer pairs HA1↔F4, HA4↔F4,and HA6↔F4 with respect to excessligand and concentration. Varying the ratio HA1:F4 (Figure 2) gave a maximum inducedhelical excess of 55% for a ratio HA1:F4 >3:1. A similar trend was observed for HA4↔F4 with a maximum value around 59% h.e. for a ratio HA4:F4 >1:1. In the case of HA6↔F4, the maximum conformational induction (around6% h.e.)was obtained with a ratio HA6:F4 = 1.2:1.In this case only, the Δδ value dropped in the presenceof an excess of HA6, falling to 0 in the presence of2.7 equiv of the ligand.

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.


Related in: MedlinePlus