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The tripeptide Arg-Gly-Asp (RGD) consists of Arginine, Glycine, and Aspartate. It was originally identified as the amino acid sequence within the extracellular matrix protein fibronectin that mediates cell attachment. The RGD cell binding sequence has since been identified in other extracellular matrix proteins, including vitronectin and laminin. The family of membrane proteins known as integrins act as receptors for these cell adhesion molecules via the RGD motif. A subset of the integrins recognize the RGD motif within their ligands, the binding of which mediates both cell-substratum and cell-cell interactions. These integrins include αvβ3, α5β1 and αIIbβ3.
The RGD domain is both sufficient and indispensable for cell membrane binding. As such, the RGD cell binding motif has supreme relevance in the fields of oncology, tissue engineering and regenerative medicine. Because of their cell-adhesive activity, RGD peptides are frequently incorporated into biomaterials designed to promote wound healing. RGD is also an important peptide sequence often used in Targeted therapy. For example, the RGD peptide can be used to target cancer cells on which cell membrane integrins are up-regulated compared to healthy cells.
Though the minimum sequence peptide RGD retains the property of cell adhesion, integrin-RGD bonds are considerably weaker than integrin-fibronectin bonds. The reduced adhesion strength is likely due to both lack of secondary structure and other synergistic domains, namely PHSRN, present in the full-length protein. Furthermore, full length protein domains differentially mediate cell morphology, cell migration and cell proliferation compared to RGD alone.
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