Lipopeptides, cyclic

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. 

One of the most characteristic features of FRET is its sensitive dependency on the fluorophore distance. This is advantageously used to evaluate structures and conformational changes of peptides, glycopeptides, and proteins among other molecules [164-166], The conformational change of the lipopeptide antibiotic daptomycin from an inactive linear form to a biological active cyclic form... 

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. 

Among the microbial surfactant producers, Bacillus subtilis strains generate a lipopeptide called surfactin, one of the most effective biosurfactants known. This biomolecule is usually a cyclic compound consisting of seven amino acids bonded to a lipid moiety. Surfactin is effective in lowering the surface tension of water to <30 dyn/cm (17), which is comparable with the values obtained by conventional synthetic surfactants. Additionally, surfactin preparations have other interesting characteristics, including antibiotic and antiviral properties (18). In fact, surfactin is one of the few biosurfactants that has found commercial use (19). 

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... 

The fungal metabolite echinocandin B (118)is one of the lipopeptides, in which a cyclic hexapeptide is combined with a long-chain fatty acid. Echinocandin B inhibits jS-l,3-glu-can synthesis and as a result has anti-Candida and anti-Pneumocystis carimi activity (149). As a group, the echinocandins are not orally bioavailable, are haemolytic, and are not very... 

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. 

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