A depsipeptide is a

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

in which one or more of its

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...

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

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

, -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 β-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, a member of the bicyclic peptide class, a known

histone deacetylase inhibitor Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that enzyme inhibitor, inhibit histone deacetylases. Since acetylation of histones, deacetylation of histones produces transcriptionally silenced heterochromatin ...

s (HDACi). It was first isolated as a fermentation product from ''Chromobacterium violaceum'' by the Fujisawa Pharmaceutical Company. Streptogramins, specifically streptogramin B antibiotics, are depsipeptides that bind to the 50S subunit of bacterial ribosomes. Etamycin 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'', from στρεπτός (''streptós''), meaning "twisted", and μύκης (''múkés''), meaning "fungus", is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of ''St ...

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

Depsipeptide natural products

References

Further reading