Depsipeptide
Encyclopedia
A depsipeptide is a peptide
in which one or more of the amide
(-CONHR-) bonds are replaced by ester
(COOR) bonds.
Depsipeptides have often been used in research to probe the importance of hydrogen bond
networks in protein folding
kinetics and thermodynamics. They are also found in nature as natural products. An infamous example is the L-Lys
-D-Ala
-D-Lac
motif found in vancomycin
resistant bacteria's cell wall building blocks. The amide
to ester
mutation disrupts its hydrogen bonding network with vancomycin, which is key its antibiotic
activity.
which is a member of the bicyclic peptide class of histone deacetylase inhibitor
s and was first isolated as a fermentation product from Chromobacterium violaceum by the Fujisawa Pharmaceutical Company. It is being used in the treatment of some cancers where it is thought to reactivate silenced genes.
The depsipeptide etamycin, a newly isolated natural product from a marine actinomycete, shows potent activity in vitro and in mice against MRSA. It was first observed to have a positive role on gene expression in 1990. A clinical trial was conducted in 1996 for T cell lymphoma.
Another natural depsipeptide HDAC inhibitor is spiruchostatin A.
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
in which one or more of the amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
(-CONHR-) bonds are replaced by ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
(COOR) bonds.
Depsipeptides have often been used in research to probe the importance of hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
networks in protein folding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
kinetics and thermodynamics. They are also found in nature as natural products. An infamous example is the L-Lys
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
-D-Ala
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
-D-Lac
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
motif found in vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
resistant bacteria's cell wall building blocks. The amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
to ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
mutation disrupts its hydrogen bonding network with vancomycin, which is key its antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
activity.
Medicine
Depsipeptide is also used to refer to romidepsinRomidepsin
Romidepsin , codenamed FK228 and FR901228, is an anticancer agent undergoing clinical trials as a treatment for cutaneous T-cell lymphoma , peripheral T-cell lymphoma, and a variety of other cancers...
which is a member of the bicyclic peptide class of histone deacetylase inhibitor
Histone deacetylase inhibitor
Histone deacetylase inhibitors are a class of compounds that interfere with the function of histone deacetylase.HDIs have a long history of use in psychiatry and neurology as mood stabilzers and anti-epileptics...
s and was first isolated as a fermentation product from Chromobacterium violaceum by the Fujisawa Pharmaceutical Company. It is being used in the treatment of some cancers where it is thought to reactivate silenced genes.
The depsipeptide etamycin, a newly isolated natural product from a marine actinomycete, shows potent activity in vitro and in mice against MRSA. It was first observed to have a positive role on gene expression in 1990. A clinical trial was conducted in 1996 for T cell lymphoma.
Another natural depsipeptide HDAC inhibitor is spiruchostatin A.