Synthesis and functional studies of THF–gramicidin hybrid ion channels

Abstract

THF-gramicidin hybrids 2-4 with the L-THF amino acid 1 in positions 11 and 12 and compounds 5-8 with the D-THF amino acid ent-1 in positions 10 and 11 were synthesized and their ion channel properties were studied by single-channel-current analysis. The replacement of positions 11 and 12 by the L-THF amino acid 1 gave a strongly reduced channel performance. In contrast, replacement of positions 10 and 11 by the D-THF amino acid ent-1 gave rise to new and interesting channel properties. For the permeability ratios, the ion selectivity shifts from Eisenman I towards Eisenman III selectivity and the channels display ms-dynamics. Most remarkable is the asymmetric compound 8, which inserts selectively into a DPhPC membrane and displays voltage-directed gating dynamics.

Detection of the activity of ion channels and pores by circular dichroism spectroscopy: G‐quartets as functional CD probes within chirogenic vesicles

“…18,19 Addition of gramicidin to EYPCLUVs ' GMP with internal K 1 and external K 1 did not cause any changes in CD (not shown). This lack of responsiveness confirmed that gramicidin does not mediate the efflux of GMP.…”

A Voltage‐Responding Ion Channel Derived by C‐Terminal Modification of Gramicidin A

“…Because heterodimer formation in vivo is unlikely, a covalent linkage of 2 and gA, for example by a succinic acid group, has to be accomplished. [15] Figure 5. Single-channel currents of 2-gA-heterodimer for different alkaline cations show an increasing voltage asymmetry from Na + to K + to Cs + .…”

Recent synthetic ion channels and pores

“…90 In ion channel 38, only amino acids 11 and 12 of the succinyl-bridged, hydrophobically capped gramicidin 32 are replaced by one artificial L-THF-d-amino acid. 91 In ion channel 39, a D-THF-d-amino acid replaces amino acids 10 and 11. In ion channel 40, one D-THF-peptide from 39 is coupled with an unchanged gramicidin scaffold.…”

“…Synthetic ion channels and pores formed by ionophoric(85,86), 'smart'(88,89) and cationic(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105) polymers of interest as antibiotics(90 -105) and for drug delivery with triggered endosomal escape(88,89).…”