In gramicidin

Hotchkiss114 isolated optically and analytically pure d-leucine from the hydrolysate. This was the first non-enzymatic proof that d-amino acids actually occurred in gramicidin. He also noted the presence of an amino-hydroxy compound, but indicated that it was not isoserine. 

James and Synge27 speculated on the nature of the nonpeptide bonds in gramicidin. 

In gramicidin SA four protons were shown to have very slow deuterium-proton exchange rates which could be assigned to specific protons. 

In this section, the general 3-sheet/ 3-turn structural motif of gramicidin S has been utilized as the basis of molecular scaffolds which can present desired sequences in (3-sheet conformations. It should be noted however that not all sequences incorporated within this template will lend themselves to forming the same 3-sheet/ 3-tum structure as found in gramicidin S. 

Hladky, S. Haydon, D.A. (1984). Ion movements in gramicidin channels. Curr. Topics in Membranes and Transport 21,327-372. 

F Leenders, J Vater, T Stein, P Franke. Characterization of the binding site of the tripeptide intermediate D-phenylalanyl L-prolyl-L-valine in gramicidin S biosynthesis. J Biol Chem 273 18011-18014, 1998. 

An additional example for the usefulness of IR spectroscopy in studying drug interactions with phospholipid vesicles is the quantitative determination of acyl chain conformation in gramicidin-DPPC mixtures [63]. The technique provides a quantitative measure of the extent to which membrane-spanning peptides induce disorder of phospholipid gel phases and order in liquid crystalline phases. 

To date, the most extensively studied natural ionophore is gramicidin,10 a polypeptide antibiotic isolated from the bacterium Bacillus brevis. Indeed, the idea of a channel-like structure for ion transport was inferred from its study. However, unlike channel proteins, which are exclusively composed of L-amino acids, each alternate amino acid in gramicidin has D-stereochemistry. It is composed of 16 residues, 15 of which are amino acids. The structure is summarized below, in which Xxx has the following identities gramicidin A (gA), Trp gB, Phe gC, Tyr gD, a mixture of gA, gB, gC, -80 5 15. 

Mackay and Wilson (1986) suggested that single-file waters in channel structures, like that studied in gramicidin A, may provide for long-range transfer of information, by a spatial (translational) response to a perturbation or by the correlated reorientation of water dipoles. 

Gramicidin S is not readily soluble in water and often precipitates in the presence of divalent counter ions (HPO4). In order to design p-sheet analogs that were more water soluble and less sensitive to salt or pH, we investigated the effect of replacing the most hydrophobic amino acid (D-Phe) in gramicidin S with a series... 

Grage, S. L., Wang, J., Cross, T. A. and Ulrich, A. S. (2002) Structure analysis of fluorine-labelled tryptophan side-chains in gramicidin A by solid state 19F-NMR. Biophysical Journal, 83, 3336-3350. 

The elucidation of a mechanism for the permeation of cations in gramicidin channels requires a complete velocity distribution for these cations in the channels. The distribution describes the fractional concentration or probability of finding an ion at a specific local velocity in the channel. An ion that moved through the channel at constant velocity would give an extremely narrow distribution 100% of the ions are moving at that single local velocity. For a discrete state model with two binding sites, the distributions could... 

Figure 4. Some typical Doppler spectra for Tl+ ions in gramicidin channels at different applied potentials. Va is the applied constant potential, and Av is the average Doppler difference frequency.

Table I. Velocities and Transit Frequencies for Tl(l) Ion in Gramicidin Channels...

Komoroski, R. A., Peat, I. R., and Levy, G. C. (1975). Biochem. Biophys. Res. Comm. 65, 272. High Field Carbon-13 nmr Spectroscopy. Conformational Mobility in Gramicidin S and Frequency Dependence of 1 3 C Spin-Lattice Relaxation Times. 

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