Bifunctional 2,5-Diketopiperazines as Rigid Three-Dimensional Scaffolds in Receptors and Peptidomimetics

• Published in: European Journal of Organic Chemistry Vol. 2011; no. 2; pp. 217 - 228
• Main Authors: Ressurreição, Ana Sofia M., Delatouche, Régis, Gennari, Cesare, Piarulli, Umberto
• Format: Book Review Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-01-2011; WILEY‐VCH Verlag; Wiley-VCH
• Subjects: Amino acids; Chemistry; Diketopiperazines; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Organic chemistry; Peptides; Peptidomimetics; Preparations and properties; Protein secondary structure; Receptors; Hairpin loop; Cyclic peptides; Amino acids; Selectivity; Characterization; Anions; Receptors; Functionalization; Three dimensional structure; Six membered ring; Helical structure; Chemical synthesis; Heterocyclic compound; Biological receptor; Molecular rigidity; Peptidomimetic compound; Bifunctional compound; Theoretical study; Secondary structure; β-Structure; Protein; Diketopiperazines; Protein secondary structure; Peptidomimetics; Aminoacid; Dipeptides; Molecular recognition; Spectrophotometry; Conformation
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201001330

2,5‐Diketopiperazines (DKPs) are heterocyclic scaffolds easily accessible from α‐amino acids and characterized by rather flat six‐membered‐ring cores that can be functionalized at four positions (N1, N4, C3, C6), two of which are stereogenic centers (C3, C6). In this microreview, the syntheses and the solution conformations of several DKP scaffolds are discussed with regard to their application as two‐armed receptors for the selective recognition of small peptides and anions and as peptidomimetics mimicking topologically relevant elements of protein secondary structure (e.g., β‐turns, β‐hairpins, and α‐helices). In many cases the properties of these compounds can be interpreted in terms of their conformationally defined three‐dimensional structures, which can be assessed by spectroscopic and computational methods.
The use of 2,5‐diketopiperazines (DKPs) in two‐armed receptors for the selective recognition of small peptides and anions and in peptidomimetics mimicking topologically relevant elements of protein secondary structure (e.g., β‐turns, β‐hairpins, and α‐helices) is reviewed.