An improved synthesis of a selective αvβ3-integrin antagonist cyclo(-RGDfK-)

The cyclic pentapeptide cyclo(-Arg-Gly-Asp-d-Phe-Lys-) is a highly potent and selective inhibitor for the αvβ3 integrin. A related compound, cyclo(-Arg-Gly-Asp-d-Phe-Val-), is a promising anticancer drug candidate; it inhibits angiogenesis and induces apoptosis in vascular cells. We have developed an improved solid-phase synthesis based on Kesslerʹs procedure to afford cyclo(-RGDfK-) peptide in high purity and high yield in a multi-gram scale. This improved synthesis is environmentally friendly and may be generally applicable to other related cyclic peptide syntheses.