Diketopiperazine receptors: A novel class of highly selective receptors for binding small peptides

A novel class of receptors consisting of a rigid diketopiperazine backbone and peptidic side chains has been developed with the use of combinatorial c hemistry. These diketopiperazine receptors interact with peptidic substrate s with high specificity as shown in combinatorial on-bead assays. The centr al diketopiperazine moiety can be easily obtained from natural 4-hydroxypro line and serves as a rigidifying template for the peptidic modules which al low for structural as well as functional variations. Screenings of several dye-marked receptor prototypes against an encoded tripeptide library demons trated not only the high binding specificities of the diketopiperazine rece ptors towards peptides but also revealed that small structural changes indu ce significant changes in their binding properties.