New Cyclic Arg-Gly-Asp Pseudopentapeptide Containing the β-Turn Mimetic GPTM

The solid-phase synthesis of cyclic pseudopeptides containing\nthe Arg-Gly-Asp recognition sequence and the dipeptide\nisostere 2-amino-3-oxotetrahydro-1H-pyrrolizine-7a(5H)-carboxylic\nacid (GPTM) was accomplished. N-Fmoc-Asp-OAll was anchored\nto Wang resin through its side chain and sequentially\ncoupled with N-Fmoc-Gly-OH, N-Fmoc-Arg(Pbf)-OH and NFmoc-\nGPTM-OH. The supported linear pentapeptide smoothly underwent\nhead-to-tail cyclization by activation with TBTU/DIPEA.\nFinally, TFA treatment released the completely deprotected cyclic\npseudopentapeptide. Competition binding assays to purified aVb3\nand aVb5 integrins showed a high inhibitory activity of cyclo[Arg-\nGly-Asp-(2S,7aS)-GPTM].