Hansen, SU, Miller, GJ ORCID: https://orcid.org/0000-0001-6533-3306, Cole, C, Rushton, G, Avizienyte, E, Jayson, GC and Gardiner, JM (2013) Tetrasaccharide iteration synthesis of a heparin-like dodecasaccharide and radiolabelling for in vivo tissue distribution studies. Nature Communications, 4 (1).

Full text not available from this repository.

Abstract

Heparin-like oligosaccharides mediate numerous important biological interactions, of which many are implicated in various diseases. Synthetic improvements are central to the development of such oligosaccharides as therapeutics and, in addition, there are no methods to elucidate the pharmacokinetics of structurally defined heparin-like oligosaccharides. Here we report an efficient two-cycle [4+4+4] tetrasaccharide-iteration-based approach for rapid chemical synthesis of a structurally defined heparin-related dodecasaccharide, combined with the incorporation of a latent aldehyde tag, unmasked in the final step of chemical synthesis, providing a generic end group for labelling/conjugation. We exploit this latent aldehyde tag for 3H radiolabelling to provide the first example of this kind of agent for monitoring in vivo tissue distribution and in vivo stability of a biologically active, structurally defined heparin related dodecasaccharide. Such studies are critical for the development of related saccharide therapeutics, and the data here establish that a biologically active, synthetic, heparin-like dodecasaccharide provides good organ distribution, and serum lifetimes relevant to developing future oligosaccharide therapeutics.

Item Type: Article
Uncontrolled Keywords: Kidney, Animals, Mice, Mice, SCID, Tritium, Heparin, Oligosaccharides, Chromatography, Gel, Chromatography, High Pressure Liquid, Magnetic Resonance Spectroscopy, Reproducibility of Results, Isotope Labeling, Tissue Distribution, Female
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Natural Sciences > School of Physical and Geographical Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 26 Nov 2015 09:40
Last Modified: 24 May 2019 14:54
URI: http://eprints.keele.ac.uk/id/eprint/1230

Actions (login required)

View Item View Item