A diketopiperazine (DKP), also known as a ''dioxopiperazine'' or ''piperazinedione'', is a class of organic compounds related to

piperazine Piperazine () is an organic compound with the formula . In term of its structure, it can be described as cyclohexane with the 1- and 4-CH2 groups replaced by NH. Piperazine exists as deliquescent solid with a saline taste. Piperazine is freely sol ...

but containing two

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 ...

linkages. DKP's are the smallest known class of cyclic peptide. Despite their name, they are not ketones, but amides. Three regioisomers are possible, differing in the locations of the

carbonyl In organic chemistry, a carbonyl group is a functional group with the formula , composed of a carbon atom double bond, double-bonded to an oxygen atom, and it is divalent at the C atom. It is common to several classes of organic compounds (such a ...

groups.

* One isomer is an oxamide obtained from

ethylenediamine Ethylenediamine (abbreviated as en when a ligand) is the organic compound with the formula C2H4(NH2)2. This colorless liquid with an ammonia-like odor is a basic amine. It is a widely used building block in chemical synthesis, with approximately ...

. * 2,5-Diketopiperazines are cyclodipeptides often obtainable via condensation of two α-

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

. * 2,6-Diketopiperazines may be viewed as cyclized

imide In organic chemistry, an imide is a functional group consisting of two acyl groups bound to nitrogen. The compounds are structurally related to acid anhydrides, although imides are more resistant to hydrolysis. In terms of commercial applications ...

derivatives derived from iminodiacetic acids. Of these three isomeric diketopiperazines, the 2,5-derivatives have attracted the greatest interest. Due to their appearance in biologically active

natural products A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical s ...

, medicinal chemists have been inspired to use DKPs to circumvent the poor physical and metabolic properties of peptides in the course of

drug discovery In the fields of medicine, biotechnology, and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or ...

Natural sources

DKPs are synthesized by a wide range of organisms, including bacteria, fungi, more complex marine microorganisms, and even mammals. However, 90% of

gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

synthesize these molecules, making them the target of most studies.

Biological activity

DKPs have been shown to inhibit the activities of bacteria, fungi, viruses, and potentially protozoa, as well as exhibit antitumor and antiprion properties. The molecule glionitrin, for instance, proved to be very effective against methicillin-resistant ''Staphylococcus aureus'' (MRSA), in addition to four different human cancer cell lines ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

''. As antivirals, however, DPKs appear to have a poor outlook when compared to those already on the market. Despite the great potential for diversity in this class of molecules, natural DPKs containing

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

are significantly overrepresented among those known to be biologically active. There also appears to be some bias with regards to stereochemistry, as DD-stereoisomers tend to display stronger antibiotic capabilities.

References

{{Reflist Functional groups