The synthesis of alternative diketopiperazines as potential RGD mimetics

Nikolett Mihala, A. Csámpai, Janez Ilaš, Danijel Kikelj, Robert Kiss, H. Süli-Vargha

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 2006

Fingerprint

Diketopiperazines
arginine glutamate
Inhibitory Concentration 50
Esters
Cyclization
Transesterification
Aspartic Acid
Integrins
Glycine
Methanol
Arginine
Conformations
Geometry

Keywords

  • Diketopiperazine
  • Integrin receptor
  • RGD mimetics
  • Transesterification

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

The synthesis of alternative diketopiperazines as potential RGD mimetics. / Mihala, Nikolett; Csámpai, A.; Ilaš, Janez; Kikelj, Danijel; Kiss, Robert; Süli-Vargha, H.

In: Journal of Peptide Science, Vol. 12, No. 10, 10.2006, p. 663-669.

Research output: Contribution to journalArticle

Mihala, Nikolett ; Csámpai, A. ; Ilaš, Janez ; Kikelj, Danijel ; Kiss, Robert ; Süli-Vargha, H. / The synthesis of alternative diketopiperazines as potential RGD mimetics. In: Journal of Peptide Science. 2006 ; Vol. 12, No. 10. pp. 663-669.
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