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 language | English |
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Pages (from-to) | 53-59 |
Number of pages | 7 |
Journal | Journal of Peptide Science |
Volume | 11 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2005 |
Keywords
- Adhesion
- Cyclopeptide
- Deamidation
- Integrin receptor
- MD and ab initio calculation
- NGR
- NMR conformation
ASJC Scopus subject areas
- Analytical Chemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry