Depsipeptide


A depsipeptide is a peptide in which one or more of its amide, -CNHR-, groups are replaced by the corresponding ester, -COR-. 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 natural products

file:Enterobactin.svg|thumb|right|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 inhibitors. 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 in a mouse model.
Several depsipeptides from Streptomyces exhibit antimicrobial activity. These form a new, potential class of antibiotics known as acyldepsipeptides. ADEPs target and activate the casein lytic protease to initiate uncontrolled peptide and unfolded protein degradation, killing many Gram-positive bacteria.
Depsipeptides can be formed through a Passerini reaction.