Chemical Classification of Cyclic Depsipeptides

Abstract

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.

Structural Diversity and Biological Activities of Fungal Cyclic Peptides, Excluding Cyclodipeptides

“…In this review, we describe the occurrence, biological activities, structures, and potential applications of the fungal cyclic peptides and their analogs, with the exception of cyclodipeptides (called 2,5-diketopiperazines), which were previously reviewed [ 15 ]. Cyclic depsipeptides from organisms including fungi, which are a big group of cyclic peptides in which one or more amino acid is replaced by a hydroxy acid, resulting in the formation of at least one ester bond in the core ring structure, have also been reviewed [ 16 ]. The cyclic peptides containing at least one ether bond in the core ring were considered as a special group and included in this review.…”

Are injectable illegal polypeptide drugs safe? Case report demonstrating the presence of haemolytic Bacillus cereus in 2 illegal peptide drugs

“…Therefore, in order to evaluate the potential virulence of these bacteria, PCR reactions were performed for the genes encoding for the clinically most important toxins namely the emetic cyclic depsipeptide cereulide, belonging to the same class as valinomycin, 2 enterotoxic complexes (Haemolysin BL (Hbl) and non‐haemolytic enterotoxin (Nhe)), the pore‐forming haemolysin IV (known as Cytotoxin K or CytK) and 2 other enterotoxins, phosphatidylcholine specific phospholipase c and haemolysin II (potential immune suppressive effect) …”

“…Therefore, in order to evaluate the potential virulence of these bacteria, PCR reactions were performed for the genes encoding for the clinically most important toxins namely the emetic cyclic depsipeptide cereulide, belonging to the same class as valinomycin, 2 enterotoxic complexes (Haemolysin BL (Hbl) and non-haemolytic enterotoxin (Nhe)), the pore-forming haemolysin IV (known as Cytotoxin K or CytK) and 2 other enterotoxins, phosphatidylcholine specific phospholipase c and haemolysin II (potential immune suppressive effect). 32,33 As can be seen in Table 1, the bacteria in both samples were negative for the emetic peptide cereulide and the enterotoxin haemolysin II but positive for the presence of the 3 major toxins (Hbl, Nhe, and CytK) and for the gene encoding phosphatidylcholine specific phospholipase c, suggesting that this bacterial strain had the potential for haemolytic effects. Indeed, these results were confirmed with the presence of yellow discolored halo formations around the colonies, typical for β-haemolysis, on the Columbia blood agar plates Since these PCR reactions were positive for the respective amplicon, thus demonstrating the presence of the potentially pathogenic B. cereus senu stricto, the potential virulence of these bacteria was evaluated by means of PCR for the clinically most important toxin.…”

Ascidian Toxins with Potential for Drug Development

“…In cyclic depsipeptides, the ring is mainly composed of amino- and hydroxy acid residues connected by amide and ester bonds (at least one of the latter) [ 53 ]. These compounds and some alkaloids are made by the non-ribosomal peptide synthesis (NRPS) mechanism.…”