Diketopiperazines are a class of cyclic organic compound

Organic compound

An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...

s that result from peptide bond

Peptide bond

This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...

s between two amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s to form a lactam

Lactam

A lactam is a cyclic amide. Prefixes indicate how many carbon atoms are present in the ring: β-lactam , γ-lactam , δ-lactam...

. They are the smallest possible cyclic peptide

Cyclic peptide

Cyclic peptides are polypeptide chains whose amino and carboxyl termini are themselves linked together with a peptide bond that forms a circular chain. A number of cyclic peptides have been discovered in nature and they can range anywhere from just a few amino acids in length, to hundreds...

s.

A diketopiperazine was the first peptide to have its complete three-dimensional structure described, in work undertaken at Caltech by Robert Corey in the 1930s. Corey studied the cyclic anhydride of the dipeptide

Dipeptide

A dipeptide is a molecule consisting of two amino acids joined by a single peptide bond.Dipeptides are produced from polypeptides by the action of the hydrolase enzyme dipeptidyl peptidase. Dietary proteins are digested to dipeptides and amino acids, and the dipeptides are absorbed more rapidly...

 glycylglycine

Glycylglycine

Glycylglycine is the dipeptide of glycine, making it the simplest peptide.The compound was first synthesized by Emil Fischer and Ernest Fourneau in 1901 by boiling 2,5-diketopiperazine with hydrochloric acid....

.

Diketopiperazines are commonly biosynthesized

Biosynthesis

Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

 from amino acids by different organisms, including mammals, and are considered to be secondary metabolite

Secondary metabolite

Secondary metabolites are organic compounds that are not directly involved in the normal growth, development, or reproduction of an organism. Unlike primary metabolites, absence of secondary metabolities does not result in immediate death, but rather in long-term impairment of the organism's...

s. Some protease

Protease

A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

 enzymes, such as dipeptidyl peptidase

Dipeptidyl peptidase

Dipeptidyl peptidase is a type of enzyme classified under EC 3.4.14.Types include:* Cathepsin C, dipeptidyl peptidase-1* DPP3, dipeptidyl peptidase-3* Dipeptidyl peptidase-4* DPP6, dipeptidyl peptidase-6* DPP7, dipeptidyl peptidase-7...

s, cleave the terminal ends of proteins to generate dipeptides which naturally cyclize to form diketopiperazines.

Due to their rigid structure, chiral

Chirality (chemistry)

A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 nature, and varied side chain

Side chain

In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called "main chain" or backbone. The placeholder R is often used as a generic placeholder for alkyl group side chains in chemical structure diagrams. To indicate other non-carbon...

s, diketopiperazines are an attractive scaffold for drug design. Both natural and synthetic diketopiperazines have a wide variety of biological activities including antitumor, antiviral, antifungal and antibacterial activities.