title: Trivalent PEGylated platform for the conjugation of bioactive compounds.
abstract: PEGylated multivalent structures are a new class of platform for biological applications due to their biocompatibility properties. Here, we present the synthesis of a trivalent structure 1 based on poly(ethylene glycol) units (PEG) as potential synthetic multifunctional carrier molecule. To evaluate whether this PEGylated platform could be useful for the conjugation of bioactive compounds, a well-known lipopolysaccharide (LPS) inhibitor 2, developed in our laboratory, was selected to be conjugated to 1. The LPS-neutralizing activity of the resulted conjugates and precursors was established using the chromogenic Limulus amebocyte lysate (LAL) assay. The trivalent structure 1 did not show LPS-binding activity, nonconjugate LPS inhibitor 2 showed high LPS-neutralizing activity, and the trivalent conjugate 4 displayed increased LPS-neutralizing activity and a reduced toxicity profile. These results prove the efficacy of this trivalent platform as a multivalent ligand scaffold for biological applications.
authors.affiliation: Combinatorial Chemistry Unit, Barcelona Science Park, University of Barcelona, Barcelona, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Torres
authors.forename: Carlos
authors.initials: C
authors.lastname: Mas-Moruno
authors.forename: Enrique
authors.initials: E
authors.lastname: Pérez-Payá
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
mesh_terms: D000818:Animals; D002460:Cell Line; D015195:Drug Design; D008033:Limulus Test; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D008070:Lipopolysaccharides; D011092:Polyethylene Glycols