title: Synthesis of O-methylsulfonyl derivatives of D-glucose as potential alkylating agents for targeted drug delivery to the brain. Evaluation of their interaction with the human erythrocyte GLUT1 hexose transporter.
abstract: In order to obtain hydrophilic analogues of 1,4-dimethylsulfonyloxybutane (busulfan) with enhanced selectivity and improved brain penetration, we have synthesized 6-O-methylsulfonyl-D-glucose, 3-O-methylsulfonyl-D-glucose, 3,6-di-O-methylsulfonyl-D-glucose, 4-O-methylsulfonyl-D-glucose, and 4,6-di-O-methylsulfonyl-D-glucose, and we have studied their interactions with the human erythrocyte GLUT1 hexose transport system. Mesylation of OH-4 and OH-6 of glucose resulted in a slightly diminished affinity for the GLUT1 glucose transporter, whereas mesylation of OH-3 led to complete loss of affinity.
authors.affiliation: UMR 133 CNRS/Rhône-Poulenc Rorer, Laboratoire de Chimie Organique Biologique, Villejuif, France.
authors.forename: T
authors.initials: T
authors.lastname: Halmos
authors.forename: M
authors.initials: M
authors.lastname: Santarromana
authors.forename: K
authors.initials: K
authors.lastname: Antonakis
authors.forename: D
authors.initials: D
authors.lastname: Scherman
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology; D001812:Blood-Brain Barrier; D002066:Busulfan / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009004:Monosaccharide Transport Proteins / Q000097:blood* / Q000187:drug effects; D013451:Sulfonic Acids
chemical_list: D018906:Antineoplastic Agents, Alkylating; D051272:Glucose Transporter Type 1; D007202:Indicators and Reagents; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D013451:Sulfonic Acids; D002066:Busulfan; D005947:Glucose