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

piperazine Piperazine () is an organic compound that consists of a six-membered ring containing two nitrogen atoms at opposite positions in the ring. Piperazine exists as small alkaline deliquescent crystals with a saline taste. The piperazines are a broad ...

but containing two

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...

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 composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...

groups.

* One isomer is an oxamide obtained from ethylenediamine. * 2,5-Diketopiperazines are cyclodipeptides often obtainable via condensation of two α- amino acids. * 2,6-Diketopiperazines may be viewed as cyclized imide 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 sy ...

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

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 do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

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'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...

''. 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 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