Host-[2]rotaxanes as cellular transport agents.
Host-[2]rotaxanes, containing a diarginine-derivatized dibenzo-24-crown-8 (DB24C8) ether as the ring and a cyclophane pocket or an aromatic cleft as one blocking group, are cell transport agents. These hosts strongly associate with a variety of amino acids, dipeptides, and fluorophores in water (1 mM phosphate buffer, pH 7.0), DMSO, and a 75/25 (v/v) buffer to DMSO solution. All peptidic guests in all solvent systems have association constants (K(A)'s) in the range of 1 x 10(4) to 5 x 10(4) M(-)(1), whereas the K(A) range for the fluorophores is 1 x 10(4) to 9 x 10(5) M(-)(1). Association constants for the cyclophane itself, cyclophane 3, are smaller. These values are in the 1 x 10(3) to 5 x 10(3) M(-)(1) range, which shows that the rotaxane architecture is advantageous for guest binding. Cyclophane-[2]rotaxane 1 efficiently transports fluorescein and a fluorescein-protein kinase C (PKC) inhibitor into eukaryotic COS-7 cells, including the nucleus. Interestingly, cleft-[2]rotaxane 2 does not transport fluorescein as efficiently, even though the results from the fluorescence assays show that both [2]rotaxanes bind fluorescein with the same ability.
Dvornikovs
Vadims
V
Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221, USA.
House
Brian E
BE
Kaetzel
Marcia
M
Dedman
John R
JR
Smithrud
David B
DB
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002522:Chlorocebus aethiops; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004988:Ethers, Cyclic / Q000737:chemistry / Q000493:pharmacokinetics; D019793:Fluorescein / Q000737:chemistry / Q000493:pharmacokinetics; D007700:Kinetics; D008958:Models, Molecular; D043862:Rotaxanes
D002352:Carrier Proteins; D004337:Drug Carriers; D004988:Ethers, Cyclic; D043862:Rotaxanes; D001120:Arginine; D019793:Fluorescein