title: Design and syntheses of mono and multivalent mannosyl-lipoconjugates for targeted liposomal drug delivery.
abstract: Multivalent mannosyl-lipoconjugates may be of interest for glycosylation of liposomes and targeted drug delivery because the mannose specifically binds to C-type lectin receptors on the particular cells. In this paper syntheses of two types of novel O-mannosides are presented. Conjugates 1 and 2 with a COOH- and NH2-functionalized spacer and the connection to a lysine and FmocNH-PEG-COOH, are described. The coupling reactions of prepared intermediates 6 and 4 with a PEGylated-DSPE or palmitic acid, respectively, are presented. Compounds 5, mono-, 8, di- and 12, tetravalent mannosyl-lipoconjugates, were synthesized. The synthesized compounds were incorporated into liposomes and liposomal preparations featuring exposed mannose units were characterized. Carbohydrate liposomal quartz crystal microbalance based assay has been established for studying carbohydrate-lectin binding. It was demonstrated that liposomes with incorporated mannosyl-lipoconjugates were effectively recognized by Con A and have great potential to be used for targeted liposomal drug delivery systems.
authors.affiliation: University of Zagreb, Centre for Research and Knowledge Transfer in Biotechnology, Rockefellerova 10, 10000 Zagreb, Croatia.
authors.forename: Adela
authors.initials: A
authors.lastname: Štimac
authors.affiliation: Institute Rudjer BoškoviĿ, BijeniĿka cesta 54, 10000 Zagreb, Croatia.
authors.forename: Jelena TrmĿiĿ
authors.initials: JT
authors.lastname: Cvitaš
authors.affiliation: Institute Rudjer BoškoviĿ, BijeniĿka cesta 54, 10000 Zagreb, Croatia.
authors.forename: Leo
authors.initials: L
authors.lastname: Frkanec
authors.affiliation: Institute Rudjer BoškoviĿ, BijeniĿka cesta 54, 10000 Zagreb, Croatia.
authors.forename: Oliver
authors.initials: O
authors.lastname: Vugrek
authors.affiliation: University of Zagreb, Centre for Research and Knowledge Transfer in Biotechnology, Rockefellerova 10, 10000 Zagreb, Croatia. Electronic address: rfrkanec@unizg.hr.
authors.forename: Ruža
authors.initials: R
authors.lastname: Frkanec
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D008081:Liposomes; D008358:Mannose / Q000008:administration & dosage / Q000138:chemical synthesis*; D008362:Mannosides / Q000008:administration & dosage / Q000138:chemical synthesis*; D013552:Swine
chemical_list: D008081:Liposomes; D008362:Mannosides; D008358:Mannose
keywords: Glycolipids; Liposomes; Mannose receptor; Targeted drug delivery