Linear Trifluoroethylamine RGD Peptidomimetics: Stereoselective Synthesis and Integrin alphavbeta3 affinity

Monica Piras, Ian N. Fleming, William T. A. Harrison, Matteo Zanda

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The Arg-Gly-Asp (RGD) tripeptide is the smallest recognition sequence for the avß3 integrin receptor. A number of non-peptide analogues of the RGD linear sequence, some of them having improved pharmacological properties, have been proposed in the last two decades. In this study, the stereogenic trifluoroethylamine function was employed as peptide bond surrogate for the development of a new class of RGD peptide mimics. In fact, the trifluoroethylamine group was shown to behave as a peptide-bond surrogate maintaining the H-bond donor capacity of the NH peptide group and a CH(CF3)NH backbone angle close to the native peptide bond 120°. The trifluoroethylamine function is also known to display high metabolic stability and in some cases it positively affects ligand-receptor interactions. Two linear ¿[CH(CF3)NH]Gly-RGD diastereoisomers 8 and 9 were synthesized with good stereocontrol and submitted to biological assays. A remarkable loss in avß3 integrin affinity was observed for both compounds, suggesting that the bulky CF3 moiety is not well tolerated within the avß3 binding pocket.
Original languageEnglish
Pages (from-to)2899-2902
Number of pages4
JournalSynlett
Volume23
Issue number20
DOIs
Publication statusPublished - 2012

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Keywords

  • trifluoroethylamine
  • peptidomimetics
  • RGD
  • integrins

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