Design, synthesis, and delivery properties of novel guanidine-containing molecular transporters built on dimeric inositol scaffolds.
We have developed a novel class of synthetic molecular transporters that contain eight residues of guanidine with an inositol dimer as the scaffold. The dimers were prepared by connecting two units of myo- or scyllo-inositol via a carbonate or amide linkage, and the multiple units of the guanidine functionality were constructed on the inositol scaffold by means of peracylation with omega-aminocarboxylate derivatives of varying length. Bioassays based on confocal laser scanning microscopy and fluorescence-activated cell sorter analyses indicated that these transporters display a varying degree of membrane translocating ability, and the intracellular localization and mouse-tissue distribution studies strongly suggested that these transporters undergo substantially different mechanistic processes from those of peptide transporters reported to date. It was also shown that doxorubicin, an anticancer antibiotic, can be efficiently delivered into mouse brain by aid of this type of transporter.
Maiti
Kaustabh K
KK
Department of Chemistry, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea.
Jeon
Ock-Youm
OY
Lee
Woo Sirl
WS
Chung
Sung-Kee
SK
D000577:Amides / Q000737:chemistry; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D019556:COS Cells; D002254:Carbonates / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002522:Chlorocebus aethiops; D019281:Dimerization; D004317:Doxorubicin / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D015195:Drug Design; D019791:Guanidine / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051379:Mice; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D000577:Amides; D002254:Carbonates; D007294:Inositol; D004317:Doxorubicin; D019791:Guanidine