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

Abstract

The solid-phase synthesis of cyclic pseudopeptides con- taining the Arg-Gly-Asp recognition sequence and the dipeptide isostere 2-amino-3-oxotetrahydro-1H-pyrrolizine-7a(5H)-carboxy- lic acid (GPTM) was accomplished. N-Fmoc-Asp-OAll was an- chored to Wang resin through its side chain and sequentially coupled with N-Fmoc-Gly-OH, N-Fmoc-Arg(Pbf)-OH and N- Fmoc-GPTM-OH. The supported linear pentapeptide smoothly un- derwent head-to-tail cyclization by activation with TBTU/DIPEA. Finally, TFA treatment released the completely deprotected cyclic pseudopentapeptide. Competition binding assays to purified aVb3 and aVb5 integrins showed a high inhibitory activity of cyclo(Arg- Gly-Asp-(2S,7aS)-GPTM).