DKPcontaining

DKP-containing refers to molecules that incorporate a diketopiperazine (DKP) moiety, a six-membered heterocycle formed by the cyclization of two amino acids. The core is commonly described as 2,5-diketopiperazine, consisting of two amide groups and two nitrogens. Substituents at the ring carbons derive from the parent amino acids, giving a diverse family of compounds with varied biological and chemical properties.

The DKP ring is relatively rigid and planar, with limited rotation around the amide bonds. This conformational constraint makes DKP-containing structures useful as peptide isosteres and scaffolds in medicinal chemistry. They often exhibit significant hydrogen-bonding capacity and can participate in hydrophobic and aromatic interactions depending on side-chain substitutions.

DKP-containing molecules occur in natural products, including fungal and bacterial metabolites, and are widely used as synthetic building blocks in drug discovery. The DKP core provides a compact, biocompatible framework that can improve metabolic stability relative to simple dipeptides, while preserving key spatial features of dipeptide chains.

Synthesis of DKP-containing compounds typically proceeds via cyclization of dipeptides (cyclodehydration) to form the DKP ring, using reagents such as carbodiimides, phosphoryl chlorides, or thionyl derivatives, often under thermal or acidic conditions. Alternative routes include cyclization of dipeptidyl precursors or enzymatic methods, and increasingly, microwave-assisted protocols to improve efficiency.

Applications of DKP-containing molecules span antimicrobial, anticancer, and central nervous system targets. They are valued for conformational control, ease of functionalization, and utility as peptidomimetics in lead optimization.