A depsipeptide is a

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

in which one or more of its

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

, -C(O)NHR-, groups are replaced by the corresponding

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

, -C(O)OR, Many depsipeptides have both peptide and ester linkages. Elimination of the N–H group in a peptide structure results in a decrease of H-bonding capability, which is responsible for secondary structure and folding patterns of peptides, thus inducing structural deformation of the helix and b-sheet structures. Because of decreased resonance delocalization in esters relative to amides, depsipeptides have lower rotational barriers for cis-trans isomerization and therefore they have more flexible structures than their native analogs. They are mainly found in marine and microbial natural products. Depsipeptide Principle V

Depsipeptide natural products

222px, Enterochelin is a depsipeptide that is an iron-transporter. Several depsipeptides have been found to exhibit anti-cancer properties. A depsipeptide enzyme inhibitor includes

romidepsin Romidepsin, also known as Istodax, is an anticancer agent used in cutaneous T-cell lymphoma (CTCL) and other peripheral T-cell lymphomas (PTCLs). Romidepsin is a natural product obtained from the bacterium ''Chromobacterium violaceum'', and wo ...

, a member of the bicyclic peptide class, a known

histone deacetylase inhibitor Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases. HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are bei ...

s (HDACi). It was first isolated as a fermentation product from ''Chromobacterium violaceum'' by the Fujisawa Pharmaceutical Company.

Etamycin Etamycin, also known as viridogrisein, is a cyclic peptide antibiotic isolate of marine actinomycete The Actinomycetales is an order of Actinomycetota. A member of the order is often called an actinomycete. Actinomycetales are generally gram-p ...

was shown in preliminary data in 2010 to have potent activity against

MRSA Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...

in a mouse model. Several depsipeptides from ''

Streptomyces ''Streptomyces'' is the largest genus of Actinomycetota and the type genus of the family Streptomycetaceae. Over 500 species of ''Streptomyces'' bacteria have been described. As with the other Actinomycetota, streptomycetes are gram-positive, ...

'' exhibit antimicrobial activity. These form a new, potential class of antibiotics known as acyldepsipeptides (

ADEPs ''Adeps'' may refer to: * ''Adeps'', a genus of beetles in the family Tenebrionidae Darkling beetle is the common name for members of the beetle family Tenebrionidae. The number of species in the Tenebrionidae is estimated at more than 20,000 an ...

). ADEPs target and activate the casein lytic protease ( ClpP) to initiate uncontrolled peptide and unfolded protein degradation, killing many Gram-positive bacteria. Depsipeptides can be formed through a

Passerini reaction The Passerini reaction is a chemical reaction involving an isocyanide, an aldehyde (or ketone), and a carboxylic acid to form a α- acyloxy amide. This addition reaction is one of the oldest isocyanide-based multicomponent reactions (IMCR) and wa ...

Depsipeptide natural products

References

Further reading