title: Synthesis of poly(lactide-co-glycolide-co-ε-caprolactone)-graft-mannosylated poly(ethylene oxide) copolymers by combination of "clip" and "click" chemistries.
abstract: Poly(lactide-co-glycolide) (PLGA) is extensively used in pharmaceutical applications, for example, in targeted drug delivery, because of biocompatibility and degradation rate, which is easily tuned by the copolymer composition. Nevertheless, synthesis of sugar-labeled amphiphilic copolymers with a PLGA backbone is quite a challenge because of high sensitivity to hydrolytic degradation. This Article reports on the synthesis of a new amphiphilic copolymer of PLGA grafted by mannosylated poly(ethylene oxide) (PEO). A novel building block, that is, α-methoxy-ω-alkyne PEO-clip-N-hydroxysuccinimide (NHS) ester, was prepared on purpose by photoreaction of a diazirine containing molecular clip. This PEO block was mannosylated by reaction of the NHS ester groups with an aminated sugar, that is, 2-aminoethyl-α-d-mannopyroside. Then, the alkyne ω-end-group of PEO was involved in a copper alkyne- azide coupling (CuAAC) with the pendent azides of the aliphatic copolyester. The targeted mannose-labeled poly(lactide-co-glycolide-co-ε-caprolactone)-graft-poly(ethylene oxide) copolymer was accordingly formed. Copolymerization of d,l-lactide and glycolide with α-chloro-ε-caprolactone, followed by substitution of chlorides by azides provided the azido-functional PLGA backbone. Finally, micelles of the amphiphilic mannosylated graft copolymer were prepared in water, and their interaction with Concanavalin A (ConA), a glyco-receptor protein, was studied by quartz crystal microbalance. This study concluded to the prospect of using this novel bioconjugate in targeted drug delivery.
authors.affiliation: Center for Education and Research on Macromolecules (CERM),  University of Liège , Sart-Tilman B6, B-4000 Liège, Belgium.
authors.forename: Hélène
authors.initials: H
authors.lastname: Freichels
authors.forename: Vincent
authors.initials: V
authors.lastname: Pourcelle
authors.forename: Rachel
authors.initials: R
authors.lastname: Auzély-Velty
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marchand-Brynaert
authors.forename: Christine
authors.initials: C
authors.lastname: Jérôme
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis*; D003208:Concanavalin A / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000378:metabolism*; D008823:Micelles; D015394:Molecular Structure; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis*; D011791:Quartz / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C507868:poly(glycolide-co-lactide-co-caprolactone); D003208:Concanavalin A; D011791:Quartz; D011092:Polyethylene Glycols; D008358:Mannose