Integrins constitute an important class of cell adhesion receptors responsible not only for cell-matrix adhesion but also for signaling bidirectionally across the membrane. Integrins are involved in many biological processes such as angiogenesis, thrombosis, inflammation, osteoporosis and cancer. Integrins thus play a key role in many severe human diseases. In this review we will describe recent research and development of RGD-containing integrin ligands for medical applications including drug design, radiolabeling, drug targeting, as well as biomaterial research. Many ligands have been developed for targeting the αvβ3 integrin in order to block angiogenesis or osteoporosis, but there are also other integrins like αvβ5 and α5β1 which become more and more interesting for similar purposes. αIIbβ3 constitutes a potent target in thrombosis therapy; but the search for suitable ligands is still ongoing. We will reconstruct the drug development process for these integrin subtypes considering selected examples with focus on structure based design. Different structural requirements are pointed out concerning integrin activity and particularly the selectivity towards the distinct integrin types. Furthermore, we will show recent progress in tumor and thrombosis imaging based on radiolabeled RGD-containing ligands binding αvβ3 or αIIbα3, respectively. Additionally further advances in biomaterial research are presented. We describe the coating of different implant materials with various αvβ3 recognizing ligands for the purpose of increasing cell attachment and biocompatibility.
Keywords: Biomaterial, Drug Targeting, Integrin Ligands, Radiolabeling, RGD Peptides, Structure Based Drug Design, Tumor Imaging