title: Oligocarbamate molecular transporters: design, synthesis, and biological evaluation of a new class of transporters for drug delivery.
abstract: Molecular transporters have the ability to deliver drugs and probe molecules into cells and tissues irrespective of their physical properties. We now report the design, synthesis, and biological evaluation of a new family of molecular transporters, guanidinylated oligocarbamates that enable exceptionally efficient uptake into cells and tissues. The synthesis features a solid-phase stepwise oligomerization to obtain the oligocarbamates and a single step perguanidinylation for the facile introduction of up to nine guanidinium groups. The oligocarbamate 9-mer is found to be among the most efficient transporters known, entering cells faster than even d-Arg9 and HIV-1 Tat49-57. Significantly, this new family of transporters also enables uptake into the formidable skin barrier of a probe molecule that by itself does not penetrate skin.
authors.affiliation: Department of Chemistry, Stanford University, California 94305-5080, USA. wenderp@stanford.edu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Wender
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Rothbard
authors.forename: Theodore C
authors.initials: TC
authors.lastname: Jessop
authors.forename: Erik L
authors.initials: EL
authors.lastname: Kreider
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Wylie
mesh_terms: D000818:Animals; D001710:Biotin / Q000008:administration & dosage / Q000493:pharmacokinetics; D002219:Carbamates / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D019791:Guanidine / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism; D051379:Mice; D012867:Skin / Q000378:metabolism
chemical_list: D002219:Carbamates; D004337:Drug Carriers; D001710:Biotin; D019791:Guanidine