Synthesis and activity of a folate peptide camptothecin prodrug.
A folate receptor targeted camptothecin prodrug was synthesized using a hydrophilic peptide spacer linked to folate via a releasable disulfide carbonate linker. The conjugate was found to possess high affinity for folate receptor-expressing cells and inhibited cell proliferation in human KB cells with an IC(50) of 10nM. Activity of the prodrug was completely blocked by excess folic acid, demonstrating receptor-mediated uptake.
Henne
Walter A
WA
Department of Chemistry and Purdue Cancer Center, Purdue University, West Lafayette, IN 47907, USA.
Doorneweerd
Derek D
DD
Hilgenbrink
Andrew R
AR
Kularatne
Sumith A
SA
Low
Philip S
PS
D001667:Binding, Competitive / Q000187:drug effects; D002166:Camptothecin / Q000037:antagonists & inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D002352:Carrier Proteins / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000737:chemistry*; D013237:Stereoisomerism; D013997:Time Factors
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011355:Prodrugs; D011956:Receptors, Cell Surface; D005492:Folic Acid; D002166:Camptothecin