Antibiotics gramicidin

The first structures of this kind were reported in 1993 pectate lyase G from Erwinia chrysanthemi (Yoder et al, 1993) and alkaline protease from Pseudomonas aeruginosa (Baumann et al, 1993). Based on consideration of these crystal structures, the term parallel //-helix was introduced for a fold containing three //-strands per coil, and parallel //-roll for a fold with two //-strands per coil (Baumann etal, 1993 Yoder andjurnak, 1995 Yoder et al., 1993). The epithet parallel was intended to emphasize the distinction between these folds and the previously observed helical structure of the antibiotic gramicidin which contains both l- and D-amino acids and... 

The peptide subunit was easily incorporated into lipid bilayers of liposome, as confirmed by absorption and fluorescence spectroscopy. Formation of H-bonded transmembrane channel structure was confirmed by FT IR measurement, which suggests the formation of a tight H-bond network in phosphatidylcholine liposomes. Liposomes were first prepared to make the inside pH 6.5 and the outside pH 5.5. Then the addition of the peptide to such liposomal suspensions caused a rapid collapse of the pH gradient. The proton transport activity was comparable to that of antibiotics gramicidin A and amphotericin B. 

Beta structures are found in many small peptides. Tire hormone oxytocin (Fig. 2-4), the antibiotics gramicidin S (Fig. 2-4) and valinomycin (Fig. 8-22), and the mushroom peptide antamanide (Box 28-B) are among these. The cyclic structures of these compounds favor formation of antiparallel (3 strands with sharp turns at the ends. Polypeptide antibiotics that have alternating... 

A parallel development came from studies on artificial lipid bilayer membranes. Hladky and Hay don (1984) found that when very small amounts of the antibiotic gramicidin were introduced into such a membrane, its conductance to electrical current flow fluctuated in a stepwise fashion. It looked as though each gramicidin molecule contained an aqueous pore that would permit the flow of monovalent cations through it. Could the ion channels of natural cell membranes act in a similar way To answer this question, it was first necessary to solve the difficult technical problem of how to record the tiny currents that must pass through single channels. 

This additive procedure was applied for the study of a number of cases including the interaction of cations with the carrier antibiotics valinomycin 184> and nonac-tin 185), the interaction of CH3NH3+ and (CH3)4N+ with amino acids mimicking the active site of a phosphorylcholine antibody186), the interaction of guanine and cytosine with amino acids 181), the interaction of Ca2+ and Mg2-1- with two serine phosphates 188), and the interaction of the channel-forming antibiotic gramicidin A with different cations 189 191>. 

Application by Titus and Fried (7) of the method to the antibiotic streptomycin, resulted in the demonstration of a second and structurally different streptomycin. When applied to the antibiotic gramicidin, two new structurally different gramicidins were found. A considerable number of other instances could be mentioned. 

We summarise recent work on computer modelling and simulation of proteins involved in bioenergetic processes and in peptide-membrane interactions. Homology modelling, electrostatic calculations and conformational analysis of a photosynthetic reaction centre protein are described. Bacteriorhodopsin, a light-driven proton pump protein is examined from several aspects, including its hydration and conformational thermodynamics. Finally, we present results on lipid perturbation on interaction with a cyclic decapeptide antibiotic, gramicidin S. 

A synthetic strategy based on the attachment to the resin of Lys/Om side chains, as reported before and on Kates on-resin cyclization method was exploited by Andreu et al. [33] for the preparation of the antibiotic gramicidin S, cyc/o(Val-Om-Leu-DPhe-Pro)2, the corresponding Lys analogue, and a further derivative containing a dipeptide surrogate of type II /3-turns, the 2-amino-3-oxohexahydroindolizino[8,7-/ ]indole-5-carboxylate system (IBTM). 

The antibiotic gramicidin S, cyc/o(LPro-LVal-LOrn-LLeu-DPhe)2, crystallized as a urea complex, has approximate twofold symmetry (Hull et ai, 1978). The backbone is elongated and twisted. There are four NH 0=C bonds across the backbone loop with the oPhe-LPro segments at either end of the elongated loop. The side groups are extended away from the backbone. 

Fig. 4 Stereo illustration of the right-handed double-stranded helieal dimer of the pentadecapeptide antibiotic gramicidin The inner channel has a diameter of approximately 4.6 A. For clarity, heavy atoms in the side chains are shown in a stick representation.

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