Oligocarbamate molecular transporters: design, synthesis, and biological evaluation of a new class of transporters for drug delivery.
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.
Wender
Paul A
PA
Department of Chemistry, Stanford University, California 94305-5080, USA. wenderp@stanford.edu
Rothbard
Jonathan B
JB
Jessop
Theodore C
TC
Kreider
Erik L
EL
Wylie
Bryan L
BL
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
D002219:Carbamates; D004337:Drug Carriers; D001710:Biotin; D019791:Guanidine