title: Synthesis and activity of a folate peptide camptothecin prodrug.
abstract: 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.
authors.affiliation: Department of Chemistry and Purdue Cancer Center, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Henne
authors.forename: Derek D
authors.initials: DD
authors.lastname: Doorneweerd
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hilgenbrink
authors.forename: Sumith A
authors.initials: SA
authors.lastname: Kularatne
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011355:Prodrugs; D011956:Receptors, Cell Surface; D005492:Folic Acid; D002166:Camptothecin