The binding of pentapeptides to biological and synthetic high affinity heparin

Ragnar Flengsrud; Simen Gjelseth Antonsen

doi:10.1016/j.bmcl.2015.07.022

The binding of pentapeptides to biological and synthetic high affinity heparin

Bioorg Med Chem Lett. 2015 Nov 1;25(21):4774-4776. doi: 10.1016/j.bmcl.2015.07.022. Epub 2015 Jul 14.

Authors

Ragnar Flengsrud¹, Simen Gjelseth Antonsen²

Affiliations

¹ Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences (NMBU), N-1432 Ås, Norway. Electronic address: ragnar.flengsrud@nmbu.no.
² Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences (NMBU), N-1432 Ås, Norway.

PMID: 26216842
DOI: 10.1016/j.bmcl.2015.07.022

Abstract

Pentapeptides have been shown to bind the synthetic heparin fondaparinux (Arixtra) as well the biological heparins dalteparin (Fragmin) and salmon heparin. In contrast to heparin binding consensus sequences, the pentapeptides are acidic or neutral, with no arginine or histidine residue. The peptides showed an effect on in vitro heparin anti-factor X activity with a reduction of fondaparinux activity by 65-95%. Heparin binding was further studied by using peptide solid phase chromatography and NMR analysis.

Keywords: Dalteparin-binding; Fondaparinux-binding; Heparin activity reversal; Heparin purification; Heparin removal; Hydrophobic interaction.

MeSH terms

Binding Sites
Dose-Response Relationship, Drug
Heparin / chemical synthesis*
Heparin / chemistry*
Molecular Structure
Oligopeptides / chemistry*
Structure-Activity Relationship

Substances

Oligopeptides
Heparin