Gramicidin peptides

Fig. 6.9 Dinuclear Zn(ll) complex of cyclic decapeptide as reported by Ka-wai et al. [53] modeled after the iono-phoric cyclic peptide gramicidin S and active in the cleavage of HPNP...

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... 

Afonin S, Durr UHN, Wadhwani P, Salgado J, Ulrich AS (2008) Solid state NMR structure analysis of the antimicrobial peptide gramicidin S in lipid membranes concentration-depen-dent re-alignment and self-assembly as a beta-barrel. Top Curr Chem 273 139-154... 

Langs, D. A. (1988). Three-dimensional structure at 0.86 A of the uncomplexed form of the transmembrane ion channel peptide gramicidin A. Science 241, 188-191. 

Solid State NMR Structure Analysis of the Antimicrobial Peptide Gramicidin S in Lipid Membranes ... 

The first successful synthesis of a biologically active cyclic peptide, gramicidin S, was accomplished by Schwyzer and Sieber[6,7l via the 4-nitrophenyl ester. The fact that -protected peptide esters can be deprotected to give the peptide active ester salts has made this approach popular not only in the synthesis of sequential polypeptides but also of cyclic peptides. Among the various active esters examined for this purpose, the pentafluorophenyl esters have emerged as the most reactive ones, although a high risk of epimerization is encountered when C-terminal chiral amino acids are involved. 

Ripka et al.[167 168l suggested that benzodiazepines of the type 138 (Scheme 52, experimental details given below) could serve as a mimetic of a (3-turn. This mimetic was incorporated into a cyclic octapeptide -containing analogue of the antibiotic peptide gramicidin S to provide 139 (Scheme 53). 

P i Izumiya, N. Kato, T. Aoyagi, H. Waki, M. Kondo, M., Synthetic Aspects of Biologically Active Cyclic Peptides Gramicidin S and Tyr-ocidines, Halsted New York, (1979) pp 16, 47. P41 Schwyzer, R. Sieber, P., Helv. Chim. Acta,... 

The linear peptide gramicidin A (15 residues) dimerizes in biological and synthetic membranes in a head-to-head manner30 to give channels of about 5 A in diameter and 32 A in length. These channels are specific for alkali metal cations, and show high transport rates, e.g. 107 Na+ ions s l, a value close to the ion fluxes found for the Na+ channel of nerve cells. Each structural unit appears to contain two channels, each of which contains two binding sites for cations. 

Particle induced desorption methods are commonly used to ionize low-volatility compounds. Cesium ion desorption (or cesium ion secondary ion mass spectrometry, SIMS) uses a primary beam of cesium ions to desorb and ionize a non-volatile sample. This technique has been used with FTMS to produce pseudomolecular ions of vitamin B12, ((812)2 + Cs - 2CN +, at m/z 2792 (24) and molecular ions of beta-cyclodextrin (m/z 1135) (92, 93). Detection limits of 10"13 mol for the peptide gramicidin S has been demonstrated using Cs+ SIMS with FTMS (25), and additional structural information was obtained using MS/MS processes. 

Shamby et al. described a surface finish that consists of a water-insoluble composite of silver bromide nanoparticles and poly(4-vinylpyridinium) salts. Again, silver is released and the quarternary ammonium groups kill on contact [139], Gyomard et al. incorporated the natural antimicrobial peptide gramicidin A into a LbL matrix and were able to show, that the peptide kills Enterococcus faecalis in the surroundings when released and on the surface in immobilized form [140], It is also possible that the antimicrobial a-poly-L-lysine in the LbL layer helped a little. 

Prenner EJ, Lewis RNAH, McElhaney RN. The interaction of the antimicrobial peptide gramicidin S with lipid bilayer model and biological membranes. Biochim. Biophys. Acta 1999 1462 201-221. Papahadjonponlos D, Moscarello M, Eylar EH, Isaac T. Effects of proteins on thermotropic phase transitions of phospholipid membranes. Biochim. Biophys. Acta 1975 401 317-335. 

Given the limitations of the above systems, it is apparent that the optimal peptide model of a p-sheet (and a p-turn) should be as analagous to the monomeric helix models as possible. In particular, the ideal p-sheet model should be small (< 20 residues), monomeric, water-soluble, pure (composed of only p-sheets and p-turns), amphipathic (to investigate sidedness), reversibly denaturable, composed of only natural amino acids, easily synthesized and easily characterized by standard spectroscopic techniques. We believe that we have developed such a peptide model. It is based on the naturally occurring cyclic peptide gramicidin S, an antibiotic produced by the bacterium bacillus brevis (12). The schematic structure of gramicidin S as determined by X-ray and NMR studies (13, 14) is shown in Figure 1. 

Two molecules of the ion-channel-forming peptide gramicidin, which contains alternating L- and D-amino acids, have been shown to form a membrane-spanning P-helix. The alternation of L- and D-amino acids is a feature of a series of cyclic peptides that self-assemble into membrane spanning nanotubes. P-Helices have now also been shown to occur as a structural element in proteins consisting only of L-a-amino acids, viz. in the enzyme pectate lyase. Related to the naturally... 

In another strategy developed by Legendre and Szoka (65), the cationic peptides gramicidin S and tyrocidine are combined with DOPE (5 1 lipid peptide ratio). Complex formation was promoted by simple mixing of the peptide (2 mg/mL) with DNA (20 pg in 300 pL) in 30 mM Tris-HCl (pH 8.5), followed by addition... 

The mixture of peptides referred to as gramicidins or gramicidin D is composed of a mixture of gramicidin A (e.g., valine-gramicidin A (58)), B, and C-type linear pentapeptides and other cyclic peptides. Gramicidins form dimeric complexes that create channels that allow protons, K, and other monovalent cations to rapidly transverse mitochondrial membranes and other lipid bilayers. ... 

The two major peptide fragments must be joined in a manner that is consistent with all the data, that is the Leu Phe Pro Val Orn Leu sequence must be con-tinous throughout the molecule. Hence the cyclic deca-peptide. Gramicidin S, has the structure of... 

In some other peptides, the cyclic structure is formed by the peptide bonds themselves. Two cyclic decapeptides (peptides containing 10 amino acid residues) produced by the bacterium Bacillus brevis are interesting examples. Both of these peptides, gramicidin S and tyrocidine A, are antibiotics, and both contain D-amino acids as well as the more usual L-amino acids (Figure 3.14). In addition, both contain the amino acid ornithine (Orn), which does not occur in proteins, but which does play a role as a metabolic intermediate in several common pathways (Section 23.6). 

The antibiotic peptide, gramicidin, is assembled (in modern cells) without the use of RNA. Peptide bonds are formed after the amino acids are activated by attachment to sulfur on the enzyme surface. Does this suggest an alternative, or a precursor, to the RNA world described in the chapter ... 

Various chemicals cause uncoupling by increasing the permeability of the membrane to protons and other small ions. Detergents, which destabilize the membrane structure, can have this effect [15]. Several small molecules, including some classical uncouplers, have been described as affecting the membrane permeability transition (MPT), which causes a dramatic increase in the ability of ions to move across the membrane [9, 16, 17]. More specific effects that increase the permeability of the membrane to protons, as caused by the peptide gramicidin A, also lead to uncoupling [14, 18, 19]. 

The performance of FAIMS trap (also called t-FAIMS ) has been evaluated for ions of doubly protonated peptide gramicidin S prefiltered by cylindrical FAIMS. The key kinetic metrics of any trap are the half-times of fill (t ) and storage (t t)—the times needed to fill an empty trap to half its capacity and for the ion population in a closed trap to halve. One normally desires to minimize and maximize t t. The ion loss due to diffusion follows the first-order kinetics (the loss per unit time is proportional to the number density N), leading to ... 

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