RGD peptide

Arginylglycylaspartic acid (RGD) is the most common peptide motif responsible for cell adhesion to the extracellular matrix (ECM), found in species ranging from Drosophila to humans. Cell adhesion proteins called integrins recognize and bind to this sequence, which is found within many matrix proteins, including fibronectin, fibrinogen, vitronectin, osteopontin, and several other adhesive extracellular matrix proteins. Arginylglycylaspartic acid (RGD) is the most common peptide motif responsible for cell adhesion to the extracellular matrix (ECM), found in species ranging from Drosophila to humans. Cell adhesion proteins called integrins recognize and bind to this sequence, which is found within many matrix proteins, including fibronectin, fibrinogen, vitronectin, osteopontin, and several other adhesive extracellular matrix proteins. RGD was identified as the minimal recognition sequence within fibronectin required for cell attachment by Ruoslahti and Pierschbacher in the early 1980s. These foundational studies also identified of the cellular receptors that recognize the sequence; these receptors were later named integrins. The RGD motif is presented in a slightly different ways in different proteins, making it possible for the many RGD-binding integrins to selectively distinguish individual adhesion proteins. Understanding of the molecular basis of binding to integrins has enabled the development of several drugs for cardiovascular disease and cancer, including eptifibatide, tirofiban, cilengitide, and the PET radiotracer fluciclatide. Eptifibatide and tirofiban are anti-clotting drugs indicated to prevent thrombosis in acute ischemic coronary syndromes. They block activation of the integrin responsible for aggregation of platelets (αIIbβ3, also known as glycoprotein IIb/IIIa) in response to the blood glycoproteins fibrinogen and von Willebrand factor. Eptifibatide (marketed as Integrilin) is a cyclic (circular) seven amino acid peptide, whereas tirofiban is a small molecule designed to mimic the chemistry and binding affinity of the RGD sequence. Cilengitide, a cyclic tetrapeptide (RGDfV), is an investigational drug intended to block the growth of new blood vessels in tumors by interfering with the activation of integrin αVβ3. It has been evaluated for the treatment of glioblastoma, but, as is the case for other anti-angiogenic therapies, has not been shown to alter progression or improve survival either alone or in combination with standard treatments. Fluciclatide, an 18F-labelled small peptide that binds to integrin αVβ3 and integrin αVβ5, is being tested as a tool to monitor treatment response of tumors to anti-angiogenic therapies. RGD-based peptides have found many applications in biological research and medical devices. Culture plates coated with peptides mimicking ECM proteins’ adhesion motifs, which restrict the differentiation of stem and progenitor cells, are on the market. RGD-coated implantable medical devices are under active study to enhance attachment of endothelial cells, which would help avoid the foreign body reaction. RGD is also a universally used tool in the construction of multifunctional “smart” materials, such as tumor-targeted nanoparticles.