Blocker efflux through blocked pores

Abstract

The objective of this paper is to clarify a frequent confusion that occurs with synthetic multifunctional pores: does molecular recognition by a synthetic pore exclude molecular translocation through the same pore? Evidence that this is not the case is provided with a set of competitive experiments using a rigid‐rod β‐barrel with internal histidine–arginine dyads as synthetic multifunctional pores (SMPs) as well as 8‐hydroxypyrene‐1,3,6‐trisulfonate (HPTS) as a fluorescent and 1,3,6,8‐pyrenetetrasulfonate (PTS) as a non‐fluorescent blocker. Direct evidence for the efflux of HPTS blockers through blocked SMPs is obtained by quenching of released HPTS with an externally added quencher. Blockage of blocker efflux through blocked pores was demonstrated by adding PTS as the opposing external blocker (KD = 3.3 μM). A Hill coefficient of n = 1.5 may indicate that binding of more than one PTS blocker is necessary to inhibit the efflux of HPTS blockers. Supported by structural information on blockage and selectivity from biological potassium channels, blocker efflux through blocked pores is discussed as being implicated in selectivity. Copyright © 2004 John Wiley & Sons, Ltd.

Molecular Recognition by Synthetic Multifunctional Pores in Practice: Are Structural Studies Really Helpful?

“…Such inducible blocker selectivity was demonstrated to occur and to be of highest importance for many applications of molecular recognition by synthetic multifunctional pores. [26] Moreover, analogous voltage dependence was predicted and confirmed, to allow for remote control of catalysis within synthetic catalytic pores. [18] Finally, the contraction of active sites toward the middle of synthetic multifunctional pores (i.e., increase of l W ) should increase the voltage dependence of molecular recognition by synthetic multifunctional pores; rigid-rod {242}-b-barrels 96 with four "active" b-strands that are sandwiched by two "inactive" b-strands at both sides are currently being synthesized to test this hypothesis.…”

“…Moreover, new pore characteristics may emerge from guest recognition. Realized examples display inversion of ion selectivity (e.g., anionic pore 2 with internal Mg 2+ becomes anion selective, cationic pore 5 with internal phosphate, cation selective), [12,20] induction of selective transport of guest compounds, [26] and pH insensitivity (pore 7 with external "cushions"). [31] The rich collection of recognized guests includes carbohydrates, inositols, nucleotides, and higher aromatics such as fullerenes, calixarenes, pyrenes, naphthalenes, and p-oligophenylenes; macromolecules such as polypeptides, polysaccharides, oligonucleotides, and polyacetylenes; and supramacromolecules such as B-DNA.…”

The Characterization of Synthetic Ion Channels and Pores

“…[38] This same supramolecular solution of the dilemma of "selectivity without loss in speed" is applicable to the selective transport of protons on the one hand [11] and that of molecules through large synthetic multifunctional pores on the other). [39] Anomalous mole fraction behavior can be used to imply multiple electrolyte binding. [6,[33][34][35] Multiply charged synthetic ion channels and pores can scavenge and permanently immobilize counterions.…”

AFM Snapshots of Synthetic Multifunctional Pores with Polyacetylene Blockers: Pseudorotaxanes and Template Effects

“…Although the clearly different conditions call for cautious interpretation, [4] it can be considered as structural support for the possibility of blocker efflux through blocked, "blockerselective" pores, a concept central to the understanding of synthetic multifunctional pores that has been verified previously at the functional level. [17] Predicted [4] and supported in silico, the nonstatistical object height distribution can be considered, with similar caution, as the so far elusive structural evidence for guest templation during molecular recognition by synthetic multifunctional pores. .…”