The structure and total synthesis of valinomycin

Shemyakin, M. M.; Aldanova, N.A.; Vinogradova, E. I.; Feigina, M.Yu.

doi:10.1016/s0040-4039(01)90943-8

Cited by 91 publications

(14 citation statements)

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“…Valinomycin is a hydrophobic antibiotic that can carry potassium ions through biological membranes. [1,2] The molecule is cyclic, and contains twelve acids with a threefold repeating motif, (l-Lac-l-Val-d-Hiv-d-Val) 3 , where Val, Hiv, and Lac are valine, a-hydroxyisovaleric acid, and lactic acid, respectively. The backbone geometry is very similar to a peptide chain because of the similarity of the amide and ester linkages.…”

Section: Introductionmentioning

confidence: 99%

Monitoring the Backbone Conformation of Valinomycin by Raman Optical Activity

2011

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Raman optical activity (ROA) spectroscopy is used to investigate the backbone conformation of valinomycin in methanol and dioxane solution. Experimental Raman and ROA spectral differences are interpreted by using density functional calculations, molecular dynamics, and Cartesian tensor transfer. Of the several conformers with different numbers of intramolecular hydrogen bonds which were preselected by calculations of relative energies, the dominant ones are identified on the basis of ROA. To separate the backbone signal from that of the side chains, conformational search for the isopropyl residues is performed for each backbone conformer. In dioxane, the most populated conformer does not exhibit C(3) symmetry, but adopts a distorted "bracelet" structure, similar to a crystal structure. This complements previous NMR spectroscopic results that could not distinguish the nonsymmetric structures. In methanol, a different, "propeller" conformer is indicated by ROA, which has three loops resembling a standard β-turn peptide motif. Molecular dynamics simulations suggest that the propeller structure is very flexible in methanol. Spectra simulated for geometries not having the β-turn do not agree with experiment. On the basis of these results, a distinct +/- ROA couplet at ∼1335/1317 cm(-1) observed in the extended amide III region is assigned to a turn in the valinomycin backbone.

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Section: Introductionmentioning

confidence: 99%

Monitoring the Backbone Conformation of Valinomycin by Raman Optical Activity

2011

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“…Valinomycin is a cyclic depsipeptide antibiotic (1,2) that acts by greatly increasing the permeability of membranes, specifically to potassium ions (3). Membranes whose permeability to potassium is altered by valinomycin include bacterial (3)(4)(5), erythrocyte (6)(7)(8), mitochondrial (9), and artificial black lipid membranes (10).…”

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confidence: 99%

Valinomycin-Induced Uptake of Potassium in Membrane Vesicles from Escherichia coli

Bhattacharyya

Epstein

Silver

1971

Proc. Natl. Acad. Sci. U.S.A.

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Osmotically shocked Escherichia coli and membrane vesicle ghosts from E. coli cells have lost the ability to accumulate potassium by active transport. The addition of valinomycin to the membrane ghosts restores the capacity to accumulate radioactive 42K and 86Rb by a temperature-and energy-dependent process. Membrane vesicles prepared from mutants of E. coli altered in potassium transport show defects in the valinomycin-stimulated accumulation of 42K that are related to the defects in the intact cells.Valinomycin is a cyclic depsipeptide antibiotic (1, 2) that acts by greatly increasing the permeability of membranes, specifically to potassium ions (3). Membranes whose permeability to potassium is altered by valinomycin include bacterial (3-5), erythrocyte (6-8), mitochondrial (9), and artificial black lipid membranes (10). The change is highly specific: only permeability to potassium and the related alkaline cations rubidium and cesium is affected (7, 10). The membranes remain impermeable to protons, sodium, lithium, and other ions in the presence of valinomycin. Evidence from relatively thick artificial membranes shows that valinomycin acts not by forming channels or pores through which potassium can travel, but by forming one-to-one complexes with K+ ions (8) which can then diffuse across the hydrophobic lipid membranes, with the K+ sheltered from the membrane within the cyclic folds of the valinomycin molecule (2). With mitochondria, at least, valinomycin facilitates the net accumulation of potassium (9) and this finding has led to models of valinomycin as a prototype for natural carriers of potassium in cell membranes. In this paper we present a similar finding with membranes prepared from cells of Escherichia coli-that is, valinomycin-facilitated uptake of potassium in an energy-dependent and apparently concentrative manner.E. coli has a number of advantages in the study of potassium transport because this organism possesses a transport system with high affinity for K (11,12), is able to maintain very large concentration gradients for K (13), and most of all because of the extensive knowledge of the genetics and metabolism of this organism. Lubin (14) first isolated and characterized specific potassium transport mutants in E. coli strain B. Later other potassium mutants were isolated in other E. coli strains (14-18) and Bacillus subtilis (14,19), and a number of mutants of E. coli K-12 with alterations in potassium transport have recently been isolated. A total of eight genes affecting potassium transport have been identified. One set of four closely linked kdp genes ("K+-dependent"; 15) and two other genes (trkA, trkD; "transport of K+") affect primarily uptake of potassium, while mutations in the trkB and trkC genes result in a defect in the retention of potassium (Epstein, in preparation). All these mutational defects appear to be specific for potassium because the mutants are normal in the ability to transport ,3-galactosides and proline (unpublished data). If we are to pursue the model from mit...

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“…2 (BROCKMANN and GEEREN, 1957). The synthesis of valinomycin by SHEMYAKIN et al (1963) proved that it is the cyclododecadepsipeptide, cyclo (L-Iactyl-L-valyl-D-oc-hydroxyisovaleryl-D-valylh (Fig. 1).…”

Section: Relationship Between Antibiotic Synthesis and Sporulationmentioning

confidence: 99%

Biosynthesis

1967

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All rights, especially that of translation into f oreign 1anguages, reserved. It is also forbidden to reproduce this book, either who1e or in part, by photomechanical means (photostat, microfilm and/or microcard) or by other procedure without written pennission from Springcr-Vcrlag Berlin Heide1bCig GmbH. DedicationFor most areas of scientific pursuit, there is usually that rare investigator who has the imagination to conceive ideas, who has faith in his visions, and who has the ability to critically test his concepts in the laboratory. Almost invariably, this scientist also inspires younger men to enthusiastically enter into his research program. To him should go the accolades and the recognitions of the esteem in which he is held. As only a small part of this esteem, we wish to dedicate these books to Professor SELMAN A. W AKSMAN in appreciation of his leadership and contributions in all facets of antibiotic research. PrefaceThe idea for publishing these books on the mechanism of action and on the biosynthesis of antibiotics was born of frustration in our attempts to keep abreast of the literature. Gone were the years when we were able to keep a bibliography on antibiotics and feel confident that we could find everything that was being published on this sUbject. These fields of investigation were moving forward so rapidly and were encompassing so wide a range of specialized areas in microbiology and chemistry that it was almost impossible to keep abreast of developments. In our naivete and enthusiasm, however, we were unaware that we were toying with an idea that might enmesh us, that we were creating an entity with a life of its own, that we were letting loose a Golom who instead of being our servant would be our master.That we set up ideals for these books is obvious; they would be current guides to developments and information in the areas of mechanism of action and biosynthesis of antibiotics. For almost every subject, we wished to enlist the aid of an investigator who himself had played a part in determining the nature of the phenomena that were being discussed. One concept for the books was that they include only antibiotics for which a definitive, well-documented mechanism of action or biosynthetic pathway was known. Yet, such an approach would not entirely serve the purpose we projected, for it would not encompass all of the information available in these fields of antibiotic investigations and blind searches for the original literature would still have to be made. We therefore chose to include any and all antibiotics about which some pertinent information had been published. It was obvious even at the start that such a compilation, integration, and analysis of information could never be complete unless scientific investigations ceased at the moment the last manuscript was submitted-an end that was neither desirable nor possible. An addendum was therefore included at the end of the volume and left open for the addition of new information until the last pages of the regular articles had been printed.The...

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The structure and total synthesis of valinomycin

Cited by 91 publications

References 4 publications

Monitoring the Backbone Conformation of Valinomycin by Raman Optical Activity

Monitoring the Backbone Conformation of Valinomycin by Raman Optical Activity

Valinomycin-Induced Uptake of Potassium in Membrane Vesicles from Escherichia coli

Biosynthesis

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