Design et synthèse de ligands d'intégrines alpha4 beta1 et beta2 : application à la modification de filtres industriels utilisés pour la rétention leucocytaire
(2011)
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- Authors
- Supervisors
- Marchand-Brynaert, Jacqueline
- Abstract
- (en) Leukocytes in blood products can lead to harmful « donor-receiver » reactions occurring after blood transfusion to a patient. To avoid these effects, European standards require the leukodepletion of blood products before transfusion. The method of filtration by means of non-woven materials is nowadays the most efficient process. The thesis project described in this manuscript aims at the research of improvements of filters made of polypropylene and poly(butylene terephthalate), provided by the firm MacoPharma. The retention of the leukocytes by a specific adhesion mechanism is considered. The integrins expressed on leukocytes could react with synthetic molecules, which mimic their natural ligands and are fixed on the filter surface. Different families of antagonists of the leukocyte integrins alpha4 beta1 and beta2 (modified peptides and peptidomimetics) were synthesized starting from the Leu-Asp-Val (LDV) and Leu-Leu-Gly (LLG) sequences recognized by the integrins. Most of these molecules are equipped with spacer-arms for the grafting on the filters. The activities of the compounds on the receptors were studied during several in vitro biological assays. New methods of functionalization were developed to immobilize the biomolecules on the non-wovens. The modified materials were characterized by surface and morphological analyses and then evaluated for their ability to retain the leukocytes during the filtration of whole blood.
- Affiliations
Citations
Gerard, E. (2011). Design et synthèse de ligands d’intégrines alpha4 beta1 et beta2 : application à la modification de filtres industriels utilisés pour la rétention leucocytaire. https://hdl.handle.net/2078.5/70074