Project

Improved glycoconjugate purification using temperature-controlled lectin multimers

Acronym
Lectin Multimers
Duration
01 October 2014 → 30 April 2016
Funding
Regional and community funding: Industrial Research Fund
Research disciplines
  • Medical and health sciences
    • Biomarker discovery and evaluation
    • Drug discovery and development
    • Medicinal products
    • Pharmaceutics
    • Pharmacognosy and phytochemistry
    • Pharmacology
    • Pharmacotherapy
    • Toxicology and toxinology
    • Other pharmaceutical sciences
Keywords
medical glycoproteins exosomes lectin-based affinity precipitation Glycoconjugate purification thermoresponsive lectins
 
Project description

Both glycans and lectins play essential roles in various aspects of the physiology and immunity of humans, animals, plants and micro-organisms. Binding between a single lectin molecule and a single glycan ligand (affinity) is typically very weak. Strong, biologically relevant binding is usually the result of multivalent interactions, i.e. the interaction of multiple lectins with multiple glycan ligands (avidity). Hence, multivalency is the key to strong glycan-lectin interactions.

This project aims to develop a novel, lectin-based technology for the purification of glycoconjugates. By combining the expertise of different UGent labs, thermoresponsive lectins will be designed: at lower temperatures, these lectins exist as monomers and show weak binding to glycan ligands (affinity); at higher temperatures, the lectins form multimers and show strong binding to glycan ligands (avidity). Their thermoresponsive properties make these lectins ideally suited for glycoconjugate purification via affinity precipitation, and this will be tested in 2 technical proof-of-concepts (POC), which reflect currently relevant industrial / research needs: i) purification of therapeutic glycoproteins and ii) purification of exosomes/ lentiviruses. Thermoresponsive lectin-based purification protocols will be tested, optimized and compared with the currently used purification methods for the respective glycoconjugate.

An optimized, thermoresponsive lectin-based affinity precipitation protocol can provide an easy, fast, cheap, high-performance and glycoform-specific alternative to the currently used techniques for glycoconjugate purification. It may be used as a stand-alone method for purification of glycoconjugates, but may also be included as an additional concentration/purification step in currently used purification protocols. Based on the success of the POCs, a targeted market study will be performed and potential industrial partners will be identified and contacted.