title: Altering the strength of lectin binding interactions and controlling the amount of lectin clustering using mannose/hydroxyl-functionalized dendrimers.
abstract: Protein-carbohydrate interactions play a critical role in many biological recognition events. Multivalent therapeutic agents that utilize protein-carbohydrate interactions have proven difficult to design, primarily because the fundamental requirements of protein-carbohydrate interactions are not well understood. Here, we report a systematic study of the effect on lectin binding of varying the loading of mannose surface residues on generations three through six PAMAM dendrimers. The degree of mannose functionalization was controlled by stoichiometric addition, and dendrimers were characterized using NMR and MALDI-TOF MS. Hemagglutination assays and quantitative precipitation assays were performed to determine the relative activity of the dendrimers. Using the mannose/hydroxyl-functionalized dendrimers reported here, we could systematically control both the degree of lectin clustering and the overall activity of the lectin with the dendrimer.
authors.affiliation: Department of Chemistry and Biochemistry, 108 Gaines Hall, Montana State University, Bozeman, Montana 59717, USA.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Woller
authors.forename: Eric D
authors.initials: ED
authors.lastname: Walter
authors.forename: Joel R
authors.initials: JR
authors.lastname: Morgan
authors.forename: David J
authors.initials: DJ
authors.lastname: Singel
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Cloninger
mesh_terms: D003208:Concanavalin A / Q000737:chemistry / Q000378:metabolism; D050091:Dendrimers; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000737:chemistry* / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D050091:Dendrimers; D037102:Lectins; C104700:PAMAM Starburst; D011073:Polyamines; D003208:Concanavalin A; D008358:Mannose