Cyclic RGD-Peptidomimetics Containing Bifunctional Diketopiperazine Scaffolds as New Potent Integrin Ligands

A perfect fit: The nanomolar affinity of a diketopiperazine-derived cyclic RGD-peptidomimetic for the integrin alpha-v-beta-3 receptor can be attributed to its high structural pre-organization. The trans-diketopiperazine scaffold induces an extended RGD disposition permitting all important interactions with the extracellular domain of the alpha-v-beta-3 integrin. The metal ion in the metal-ion-dependent adhesion site region is represented by a magenta sphere.