Synthesis of a lipid/peptide/drug conjugate: N4-(acylpeptidyl)-ara-C.
A lipid/peptide/drug conjugate, N4-(acylpeptidyl)-ara-C, is synthesized under mild conditions to give an ara-C prodrug protected against cytidine deaminase-catalyzed deactivation. The compounds can be bound, via their hydrocarbon tails, to phospholipid membranes and examined for chymotrypsin-induced drug release. A tripeptide is too short to permit efficient enzyme/membrane contact and subsequent freeing of the drug. Faster rates can, presumably, be achieved by "fine tuning" the length and polarity of the peptide spacer attached to the drug.
Department of Chemistry, Emory University, Atlanta, Georgia 30322.
F M
FM
Menger
Y
Y
Guo
A S
AS
Lee
D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D003564:Cytidine Deaminase / Q000378:metabolism; D007202:Indicators and Reagents; D009842:Oligopeptides / Q000138:chemical synthesis*; D011355:Prodrugs / Q000138:chemical synthesis*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D007202:Indicators and Reagents; D009842:Oligopeptides; D011355:Prodrugs; D003561:Cytarabine; D003564:Cytidine Deaminase