The synthesis of alternative diketopiperazines as potential RGD mimetics

Nikolett Mihala, Antal Csámpai, Janez Ilaš, Danijel Kikelj, Robert Kiss, Helga Süli-Vargha

Research output: Contribution to journalArticle

4 Citations (Scopus)


Alternative RGD mimetics - with the exception of glycine - c(Arg-Asp) 1, c(Arg-Glu) 2 and c[Arg-Asp(Phe-OH)] 3 were synthesized. The DKPs were prepared on solid phase with orthogonal protection allowing further derivatization in solution. During solution phase cyclization in NH3/ methanol, the side chain benzyl ester group of H-Arg(Tos)-Asp(OBzl)-OMe and H-Arg(Tos)-Glu(OBzl)-OMe suffer transesterification, while β-t-butyl or β-cyclohexyl esters are stable under the same conditions. In spite of the simple structure, all compounds bind selectively to the αvβ 3 integrin receptor, 3 showing the highest affinity with an IC50 value of 0.74 μM value. On the other hand only 3 binds with measurable activity to the α IIbβ3 receptor (IC50 159 μM). The binding affinities seem to be in accordance with the distances between the arginine guanidino and the aspartic acid carboxyl group in extended conformation determined by semiempirical geometry optimization.

Original languageEnglish
Pages (from-to)663-669
Number of pages7
JournalJournal of Peptide Science
Issue number10
Publication statusPublished - Oct 1 2006



  • Diketopiperazine
  • Integrin receptor
  • RGD mimetics
  • Transesterification

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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