title: Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity.
abstract: The interactions between chondroitin sulfate (CS) and a wide number of proteins modulate important biological processes. Here, the binding properties to midkine and pleiotrophin of sulfated, fully protected intermediates, typically obtained in the chemical synthesis of CS oligosaccharides, were tested for the first time. Using a fluorescence polarization competition experiment, we discovered that these synthetic precursors strongly bound these two closely related cytokines involved in cancer and inflammation. The relative binding affinities of these intermediates were significantly higher than those displayed by the corresponding fully deprotected oligosaccharides, indicating that the presence of hydrophobic protecting groups strongly enhanced the binding of CS-like derivatives to midkine. These compounds offer novel opportunities for the development of potent inhibitors/activators of CS-protein interactions with potential therapeutic applications.
authors.affiliation: Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), cicCartuja, CSIC and Universidad de Sevilla, Americo Vespucio, 49, 41092 Sevilla, Spain. jlpaz@iiq.csic.es pedro.nieto@iiq.csic.es.
authors.forename: J L
authors.initials: JL
authors.lastname: de Paz
authors.forename: P M
authors.initials: PM
authors.lastname: Nieto
mesh_terms: D001665:Binding Sites; D002809:Chondroitin Sulfates / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005454:Fluorescence Polarization; D057927:Hydrophobic and Hydrophilic Interactions; D000078792:Midkine
chemical_list: D016207:Cytokines; D000078792:Midkine; D002809:Chondroitin Sulfates