Synthesis and functional studies of THF-gramicidin hybrid ion channels

• Published in: Organic & biomolecular chemistry Vol. 1; no. 16; p. 2983
• Main Authors: Vescovi, Andrea, Knoll, Andrea, Koert, Ulrich
• Format: Journal Article
• Language: English
• Published: England 21-08-2003
• Subjects: Amino Acid Sequence; Cations - chemistry; Electric Conductivity; Furans - chemistry; Gramicidin - chemistry; Ion Channel Gating; Ion Channels - chemical synthesis; Ion Channels - chemistry; Lipid Bilayers - chemistry; Permeability; Phospholipids - chemistry; Protein Conformation; Structure-Activity Relationship
• ISSN: 1477-0520
• DOI: 10.1039/b303249n

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.