Synthesis and functional studies of THF-gramicidin hybrid ion channels.
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.
Vescovi
Andrea
A
Institut für Chemie, Humboldt-Universität Berlin, Brook-Taylor-Str. 2, D-12489 Berlin, Germany.
Knoll
Andrea
A
Koert
Ulrich
U
D000595:Amino Acid Sequence; D002412:Cations / Q000737:chemistry; D004553:Electric Conductivity; D005663:Furans / Q000737:chemistry*; D006096:Gramicidin / Q000737:chemistry*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000138:chemical synthesis / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D002412:Cations; D005663:Furans; D007473:Ion Channels; D008051:Lipid Bilayers; D010743:Phospholipids; D006096:Gramicidin; C018674:tetrahydrofuran