Common structural features in gramicidin and other ion channels

Simultaneous Measurements of K+ and Calcein Release from Liposomes and the Determination of Pore Size Formed in a Membrane

“…Because K + leakage is the first event in the permeabilization of a membrane, measurements of differences in the rates of release of K + and calcein, which is larger than K + , can provide significant information about the sizes of pores made by membrane-active substances. We tested various membrane-active substances; the channel-forming peptide gramicidin A, 8,9 polyene antibiotics such as amphotericin B, nystatin, and filipin, 8,10,11 antimicrobial peptides such as gramicidin S, alamethicin, and melittin, 8,9,[12][13][14] and membranedisrupting drugs such as celecoxib (non-steroidal anti-inflammatory drug), 6 1-dodecylazacycloheptan-2-one (named azone; skin permeation enhancer), 15 and chlorpromazine (tranquilizer). 16,17 Although simultaneous monitoring of the different rates of K + and calcein release from liposomes provided significant information about the sizes of pores generated by these substances, we further determined the sizes more precisely by conducting an osmotic protection experiment.…”

Creating novel protein scripts beyond natural alphabets

“…Other secondary structure patterns are much less in abundance. An unusual one, and of stereospecific nature, occurs in alternating L, D polypeptides, of alternating L-and D-chiral stereochemical structure, with gramicidin-b-helix as a major stereochemically feasible secondary structure (Szabo and Urry 1979;Urry 1971;Wallace 1998Wallace , 2000.…”

“…7 and n -5 type hydrogen bonds (Fig. 2d) and occurs in Gramicidin A, a microbial polypeptide of syndiotactic stereochemistry (Szabo and Urry 1979;Urry 1971;Wallace 1998Wallace , 2000. Extended conformation of isotactic stereochemistry, in mutually hydrogen-bonded parallel or antiparallel arrangement, characterize the b sheet motifs of proteins, in which the hydrogen bond topologies are on average [n ?…”

“…6). It adopts a range of unusual conformational folds of b-helical and double b-helical nature of both parallel and antiparallel variety, which contribute in its function as a membrane active peptide with ion channeling activity, with the main-chain amides performing the dual role of both conformation specification and ion conductance (Urry 1971;Wallace 1998Wallace , 2000. In close correspondence with this example, Ghadiri and coworkers developed a series of alternating L, D chiral cyclic peptides as self assembling nanotubes cum channels due to their b-sheet type intermolecular hydrogen bonding (Ghadiri et al 1994).…”

“…The morphological range and the architectural plans for heterotactic proteins remain to be defined, but the conceptual foundations for diversification and downsizing structure seem clear. Ghadiris nanotube's and gramicidin-A perhaps best exemplify the prospect (Ghadiri et al 1994;Urry 1971;Wallace 2000). Likewise several reported hairpin peptides and mini-proteins directed or stabilized by one or more D chiral residues are examples of downsizing achieved by de novo design (Dhanasekaran et al 1999;Durani 2008;Struthers et al 1996).…”