Cyclic lipopeptide

B. anthracis and related species.41,44 6 Some of these peaks have been identified (e.g., as small acid soluble spore proteins and cyclic lipopeptides), but others remain uncharacterized. There is no agreement among different laboratories as to which markers are suitable for chemotaxonomic differentiata-tion of species (i.e., are consistently found in one species versus another) or for strain identification (i.e., are reproducibly found in one strain but not another). Further, although it might be anticipated that surface proteins can be preferentially ionized or extracted, the ultra-structural origin of some peptides within the cell is not always clear. 

Even newer is the natural product daptomycin (Cubicin), a complex cyclic lipopeptide structure, approved for use in the United States in 2003. Daptomycin has a spectrum similar to that of linezolid and specifically includes MRSA and VRE. In contrast to linezolid, daptomycin is bactericidal for these Gram-positive organisms. It is, like vancomycin, a parenteral antibiotic and is given intravenously. It is indicated for treatment of complicated skin and skin structure infections and for some cases of bacteremia, including endocarditis. Daptomycin may be thought of as an alternative to vancomycin. 

A novel cyclic lipopeptide antibiotic was isolated from cultures of Strep-tomyces roseosporus grown in the presence of decanioc acid. Daptomycin interacts with the bacterial cell membrane and interferes with membrane potential.Unlike polymyxin B, daptomycin can target majority of clinically relevant Gram-positive pathogens. 

Iturins are a group of fungicidal cyclic lipopeptides produced by Bacillus subtilis m m m All members of this group are cyclic octapeptides with seven a-amino acids and a unique 13-amino fatty acid homologue of iturinic acid. The predominant iturin-A isomer, A2, contains the n-C14-isomer of iturinic acid (Itu) (Scheme 8). The synthesis of the molecule can be divided into two steps with the first stage consisting of the assembly of the linear octapeptide on solid phase followed by the backbone cyclization in solution. 

Bonnard, I., Rolland, M., Francisco, C, and Banaigs, B. (1997). Total structure and biological properties of laxaphycins A and B, cyclic lipopeptides from the marine cyanobacterium Lyngbya majuscula. Lett. Pept. Sci. 4, 289-292. 

Takahashi, T., Ohno, O., Ikeda, Y., Sawa, R., Homma, Y., Igarashi, M., and Umezawa, K. (2006). Inhibition of lipopolysaccharide activity by a bacterial cyclic lipopeptide surfactin. ]. Antibiot. 59, 35-43. 

Polymyxin B Bacillus polymyxa R-Dab-Thr-Dab-Dab-Dab-(D) Phe-Leu-Dab-Dab-Thr (Dab is diaminobutyric acid) Cyclic lipopeptide 1.8 26 (59-61)... 

The simultaneous deprotection of both an allyl ester and an Aloe group is a popular tactic for liberating an amino and carboxyl function prior to formation of a lactam ring. The strategy is exemplified in Scheme 8.83 en route to a derivative of the ichthyotoxic cyclic lipopeptide Antillatoxin.196... 

Recent studies on the mechanism of biosynthesis of cyclic lipopeptide antibiotics have proved that these are systematically synthesized by the multifunctional proteins, non-ribosomal peptide synthetase (NRPS). 

Cyclic lipopeptide antibiotics can be classified structurally into several groups. The enormous structural diversity in this group of antibiotics leads... 

Leucine-rich cyclic lipopeptides are mainly produced by gram-positive Bacillus spp. and gram-negative Pseudomonas fluorescens. Their structural similarity is not always reflected in their biological activity, and they exhibit some diversity in this regard. 

Cyclic lipopeptides containing piperazic acid show potent toxicity against tumor cells. This class of compounds shows potent antibacterial activity against gram-positive bacteria. The following five cyclic lipopeptides are all hexadepsipeptides and are produced by Streptomyces spp. 

Three types of guanidine-containing cyclic lipopeptides have been discovered from microbial metabolites the first group comprises plusbacins ° empedopeptin and tripropeptins the second involves fusaricidins and heptadepsin, and the third group contains... 

In this section, cyclic lipopeptides not belonging to any of the previous sections will be described. 

CYCLIC LIPOPEPTIDES FROM FUNGAL METABOLITES 2.1 Echinocandin lipopeptides... 

A lot of interesting lipopeptides, both terms of biological activities and structures, have been discovered from the metabolites of marine-associated organisms. In particular, cyanobacteria produce many kinds of bioactive metabolites including toxins and enzyme inhibitors. Some cyclic lipopeptides from marine-associated organisms have unique structures, which are much different from those of their soil-associated counterparts. For example, the a-diketo structure is in cyclotheonamides 3-amino-6-hydroxy-2-piperidone is in micropeptins, scyptolins and planktopeptins and (2S, 3S, 8S,... 

Cyclic lipopeptide antibiotics contain various kinds of amino acids including unusual amino acids. Many kinds of cyclic lipopeptides were discovered from microorganisms and they often exhibit a wide variety of biological activities such as antimicrobial, antifungal, antitumor, and enzyme inhibitory activities. It is also of considerable interest that the structural similarities do not always reflect any similarity of biological activities in the cyclic lipopeptides. 

The structural and biological diversity of the cyclic lipopeptide antibiotics is extremely attractive to chemical, pharmacological and medical sciences. Future rational drug design, chemical modification and discovery of novel cyclic lipopeptides from natural sources will give rise to useful biological tools for research and development in the medicinal sciences. 

Chemical characterization hypothesizes that certain molecules are unique and representative of individual microorganisms, and therefore the mass spectra can be characteristic of given species. A typical bacterial spectrum obtained by MALDI-TOF usually contains between 20 and 40 large peaks, mainly produced by proteins, phospholipids, and cyclic lipopeptides, in the MW range of 4—20 kDa.31 ESI is less frequently used samples containing intact cells can clog electrospray devices, and the formation of multiply charged species complicates the spectra. 

Orjala, J., Nagle, D. G., Hsu,V., Gerwick, W. H., Antillatoxin An Exceptionally Ichthyotoxic Cyclic Lipopeptide from the Tropical Cyanobacterium Lyngbya majuscule, J. Am. Chem. Soc. 1995, 117, 8281-8282. 

Total synthesis of antillatoxin, an ichthyotoxic cyclic lipopeptide from marine cyanobacterium Lyngbya majuscula 00YGK634. 

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