Solution state conformation and degradation of cyclopeptides containing an NGR motif

Anna K. Füzéry, Nikolett Mihala, Pál Szabó, András Perczel, Raffaella Giavazzi, Helga Süli-Vargha

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In contrast to the RGD-peptides, head to tail cyclization of LNGRV and LNGRv caused only a marginal change in their integrin receptor affinity as shown by the limited effect and selectivity on the adhesion of endothelial cells to ECM components. Structure determination of the two cyclopeptides by NMR and MD, semiempirical and ab initio methods revealed that both are very flexible and take on multiple stable conformers in solution. This structural diversity, along with the presence of the Asn-Gly peptide bond, enhances succinimide ring formation leading to the hydrolysis of Asn. It has been demonstrated that c(LNGRV) suffers deamidation with time both in solution and during storage. As the isoaspartyl-peptide may co-elute with the asparginyl-peptide in the course of HPLC analysis, MS measurement is necessary to check the purity of peptides containing the NGR sequence. Our stability investigations raise the question whether the NGR motif or its hydrolysis product is effective in in vivo experiments.

Original languageEnglish
Pages (from-to)53-59
Number of pages7
JournalJournal of Peptide Science
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

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Keywords

  • Adhesion
  • Cyclopeptide
  • Deamidation
  • Integrin receptor
  • MD and ab initio calculation
  • NGR
  • NMR conformation

ASJC Scopus subject areas

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

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