Interface Engineering of Synthetic Pores: Towards Hypersensitive Biosensors

Abstract

Hydrophilic anchoring is introduced as a promising strategy to constructively control the various interactions of synthetic pore sensors with the surrounding biphasic environment. Artificial rigid-rod beta barrels are selected as classical synthetic multifunctional pores and random-coil tetralysines are attached as hydrophilic anchors. The synthesis of this advanced pore is accomplished in 32 steps from commercially available starting materials. With regard to pore activity as such, the key impact of hydrophilic anchoring is a change from a Hill coefficient n<1 to n=4. This change confirms successful suppression of the competing self-assembly with precipitation from the aqueous phase as the origin of the accomplished increase in pore activity. The hydrophilic anchors do not interfere with the blockage of the synthetic pore sensors by anionic analytes. In the case of stoichiometric binding of blockers (K(D)=EC(50) of the pore; EC(50)=concentration needed to observe 50 % pore activity), however, the increase in pore activity achieved by hydrophilic anchoring results in improved pore blockage under high dilution conditions. Controls confirm that this increase does not occur with analytes that do not exhibit stoichiometric binding (K(D)>EC(50)). These results not only reveal stoichiometric binding as the expected origin of the sensitivity limit of synthetic pore sensors, they also provide promising solutions for this problem. The combination of hydrophilic anchoring with targeted pore formation emerges as a particularly promising strategy to further reduce effective pore concentrations. The scope and limitations of this approach are exemplified with pertinent analyte pairs that are essential for the sensing of sucrose, lactose, acetate, and glutamate with synthetic pores in samples from the supermarket.

Dynamic Octopus Amphiphiles as Powerful Activators of DNA Transporters: Differential Fragrance Sensing and Beyond

“…), respectively. This poor discrimination among long alkyl tails suggests that the limit of stoichiometric binding [56] is reached and activities cannot be further improved in the given assay. The pentyl tails in octopus amphiphile G1H4O5 produced a clearly reduced EC 50 = (23.8 AE 1.5) mm at preserved high (Figure 3 a, *).…”

“…The only exception from this trend was observed at EC 50 < 10 mm, at which the onset of stoichiometric binding processes obscured intrinsic differences between individual transport systems. [56] As an interesting consequence, the activity of tetrabutyl octopus amphiphile G1H4O4 was observable below the EC 50 = 100 mm threshold, whereas the corresponding G1H3O4, G1H2O4 and G1H1O4 were at EC 50 > 100 mm or fully inactive (Figure 4 a, a).…”

“…As highly dynamic minority components, all active structures are thus undetectable by routine spectroscopic methods (Figure 4 c, a). [55,56] Detection and discrimination of anisaldehyde odorants O11-O13 was one of the problems faced with the previously reported reactive cations G1H1-G1H3 and A1H1-A1H3 (Figure 5, c). This problem was rationalized with insufficient amphiphilicity.…”

Synthesis of Half‐Channels by the Anionic Polymerization of Ethylene Oxide Initiated by Modified Cyclodextrin

“…By Nezha Badi,* Loïc Auvray, and Philippe Guégan* Biomimetic synthetic pores acting as ion channels [1][2][3][4] have important applications in pharmacology and nanotechnology. For instance, they may possibly act as ideal antimicrobial agents thanks to their resistance to enzymatic degradation.…”

Synthesis of VIP-Lipopeptide Using a New Linker to Modify Liposomes: Towards the Development of a Drug Delivery System for Active Targeting

“…Indeed, selective mono-alkylation of more acidic poly-phenolic compounds with benzyl bromoacetate smoothly proceeded to give the desired product in high yield under similar conditions. 18,19) Although the yield was not satisfactory, we carried out the next step. Tosylation of 4 smoothly proceeded to give 5 (73% yield), which was reacted with azide anion to give the desired azide 6 in 84% yield (Chart 2).…”