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.
Menger
F M
FM
Department of Chemistry, Emory University, Atlanta, Georgia 30322.
Guo
Y
Y
Lee
A S
AS
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