Chemical Classification of Cyclic Depsipeptides.

Cyclic depsipeptides (CDPs) are a family of cyclic peptide-related compounds, of which the ring is mainly composed of amino- and hydroxy acid residues joined by amide and ester bonds (at least one), leading to a wide diversity of fascinating chemical structures. They differ in both their ring structure and their side chains, especially by the nature of the unusual and non-amino acid building blocks. To date, however, there is no overall uniform chemical classification system available for CDPs and naming of the diverse family members is done rather arbitrarily. Therefore, a broad evaluation of different CDP structures is done, i.e., 1348 naturally occurring CDPs were included, and a straightforward chemical classification system using apparent chemical characteristics is proposed in order to organize the currently scattered CDP data. The overall validity of the classification approach is verified and the compounds categorized in the same groups are considered to be structurally related. This evaluation also revealed that traditionally formed CDP subfamilies, like the dolastatins, might be misleading from a chemical point of view given the structural differences in this subfamily. This up-to-date CDP overview enables peptide and natural product scientists to study the wide diversity in CDP structures, their chemical interrelationships and identification of existing and newly found CDPs. Together with the available information on the species producing these CDPs and their reported biological activities, this paper provides a useful tool to gain new insights into this diverse group of peptides.

The mycotoxin definition reconsidered towards fungal cyclic depsipeptides.

Currently, next to the major classes, cyclic depsipeptides beauvericin and enniatins are also positioned as mycotoxins. However, as there are hundreds more fungal cyclic depsipeptides already identified, should these not be considered as mycotoxins as well? The current status of the mycotoxin definition revealed a lack of consistency, leading to confusion about what compounds should be called mycotoxins. Because this is of pivotal importance in risk assessment prioritization, a clear and quantitatively expressed mycotoxin definition is proposed, based on data of widely accepted mycotoxins. Finally, this definition is applied to a set of fungal cyclic depsipeptides, revealing that some of these should indeed be considered as mycotoxins.

Ulleungamides A and B, Modified α,ß-Dehydropipecolic Acid Containing Cyclic Depsipeptides from Streptomyces sp. KCB13F003.

Two novel cyclic depsipeptides, ulleungamides A (1) and B (2), were isolated from cultures of terrestrial Streptomyces sp. Their structures were determined by analyses of spectroscopic data and various chemical transformations, including modified Mosher's method, advanced Marfey's method, PGME, GITC derivatizations, and Snatzke's method. Ulleungamides were determined to be a new class of peptides bearing unprecedented units, such as 5-hydroxy-6-methyl-2,3-dehydropipecolic acid, 4,5-dihydroxy-6-methyl-2,3-dehydropipecolic acid, and amino-linked 2-isopropylsuccinic acid. Ulleungamide A displayed growth inhibitory activity against Staphylococcus aureus and Salmonella typhimurium without cytotoxicity.

PPZPMs--a novel group of cyclic lipodepsipeptides produced by the Phytophthora alni associated strain Pseudomonas sp. JX090307--the missing link between the viscosin and amphisin group.

The closely related to the Pseudomonas orientalis strain Pseudomonas sp. acc. no. JX090307 was isolated from hyphae of the phytopathogenic oomycete Phytophthora alni spp. alni. In in-vitro antagonistic tests, the living bacterium JX090307 and its cell extract showed antibiosis activity against different fungal pathogens of forest tree species, particularly against Verticillium dahliae and some strains of P. alni ssp. alni. Investigating the cell extract of JX090307 by means of LC-ESI-Q-TOF-MS and -MS/MS techniques, more than 30 cyclic lipodepsipeptids (CLPs) were found. 24 of them belong to a novel group of CLPs named PPZPM. The cyclic lipodepsidecapeptides PPZPMs are composed of a beta-hydroxy fatty acid linked to a peptide part comprising 10 amino acids, where 8 of them are organized in a cyclic structure. PPZPMs differ from members of the Viscosin and Amphisin group by the number of amino acids forming the cyclic structure. The two main components, PPZPM-1a and PPZPM-2a, were investigated additionally by means of NMR spectroscopy.

Acaricidal action of destruxins produced by a marine-derived Beauveria felina on the bovine tick Rhipicephalus (Boophilus) microplus.

The increasing resistance of Rhipicephalus (Boophilus) microplus tick to commercial insecticides requires alternative methods for the control of this cattle plague. The enthomopathogenic fungus Beauveria felina produces destruxins in culture media, cyclic depsipeptides which display an array of biological activities. The present investigation aimed to evaluate the acaricide action of destruxins isolated from B. felina culture media on R. (B.) microplus engorged females. B. felina was grown in MF medium under 19 different growth conditions. HPLC-PDA analysis of chromatographic fractions obtained from the 19 different growth media extracts indicated the presence of destruxins in all lipophylic fractions. Such fractions were combined and subjected to separation by HPLC. Fractions containing distinct destruxins composition were tested against R. (B.) microplus. Two fractions, composed of destruxin Ed(1) and pseudodestruxin B and/or pseudodestruxin C (fraction P1) as well as by hydroxyhomodestruxin B and/or destruxin D and/or roseotoxin C (fraction P7), displayed 30% and 28.7% acaricidal efficacy, respectively. This activity profile in such low concentration is adequate to consider destruxins as potential leading compounds to be developed for tick biological control.

Synthesis and cytotoxicity of a new class of potent decapeptide macrocycles.

Described are the syntheses of five decapeptides that are C-2-symmetrical derivatives of the natural product pentapeptide sansalvamide A. Derivatives were made using a succinct convergent synthesis. These analogues share no structural homology to current cancer drugs, are cytotoxic at levels on par with existing drugs treating cancers, and demonstrate selectivity for drug-resistant pancreatic cancer cell lines over noncancerous cell lines. These molecules are excellent chemotherapeutic leads in the search for new anticancer agents.