Peptides from gramicidin

A second group of ionophores are considered to promote the formation of cylindrical channels through the membrane. The cation diffuses through the channel from one membrane surface to the other. The known channel-forming ionophores (the open-chain peptide derivative, gramicidin A, is one example) are non-cyclic species and, as such, lie outside the scope of this discussion. 

In order to establish structural constraints on proteins and peptides from solid-state NMR, it is important to consider all aspects from appropriate labeling of the sample, selection of the experiments providing the desired information, and to have appropriate reference data available to allow extraction of structural data from the (anisotropic interaction) parameters determined by the experiment. As an example. Cross and co-workers investigated the conformation of the ion channel gramicidin A using selectively N-labeled peptides in uniaxiaUy oriented lipid bilayers c.f.. Section 4.2). To translate the measured " N chemical shifts in the oriented samples into stractural constraints, it is necessary to determine the magnitude and orientation of the " N chemical shift tensors... 

Test samples consisted of peptide solution. Gramicidin S samples were prepared starting from a stock solution at 0.1 mM in a MeOH H20 50 50 mixture acidified with 0.1 % formic acid the concentration range of Gramicidin S was of 50 down to 1 pM. 

Typically, the insertion induces sharp variation of the membrane profile at the distances 0.5-1.0nm from the membrane-peptide interface [79-82]. The steepness of this perturbation indicates that the short-A, behavior of membrane moduli must be important in the estimates of the elastic energy. In addition, a peptide inserted in a membrane almost certainly perturbs the membrane s elastic moduli in the immediate vicinity of the inclusion. Both these effects, membrane nonlocality and nonuniform modification of elastic properties by insertions, might play an important role in resolving the contradiction between the local calculations [80] and the experimental data for the mean lifetime of a gramicidin channel [81,109,110]. ... 

Salgado J, Grage SL, Kondejewski LH, Hodges RS, McElhaney RN, Ulrich AS (2001) Membrane-bound structure and alignment of the antimicrobial beta-sheet peptide gramicidin S derived from angular and distance constraints by solid state F-19-NMR. J Biomol NMR 21 191-208... 

Similarly, iterative NRPSs operate in a linear fashion but utilize at least one domain or module multiple times for the synthesis of a single NRP product. Thus, peptides assembled by iterative synthetases contain short, repeating units of peptide building blocks. In such systems, the terminal PCP-TE (or infrequendy PCP-C) didomain is responsible for both condensation of the repeating peptide units and chain release from the assembly line. NRPs biosynthesized in this manner include enniatin, enterobactin, bacillibactin, " gramicidin and the depsi-peptides valinomycin and cereulide. Of these examples, condensation of the precursor peptides for both enterobactin and gramicidin S has been extensively studied and will be discussed in detail. 

Fig.l Chemical structure of the gramicidin S analogue GS-3/3 with 4F-Phg (Fluorine atom is marked red) substituted for Leu3/Leu3 and N-labeled Vall/Vall (Nitrogen atom is marked blue). The peptide is displayed from one hydrophilic surface (A) and from one side (B) to define the molecular axis system used in the structure analysis... 

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