Synthesis and activity of a folate targeted monodisperse PEG camptothecin conjugate

Walter A Henne; Sumith A Kularatne; John Hakenjos; Joshua D Carron; Kristene L Henne

doi:10.1016/j.bmcl.2013.08.113

Synthesis and activity of a folate targeted monodisperse PEG camptothecin conjugate

Bioorg Med Chem Lett. 2013 Nov 1;23(21):5810-3. doi: 10.1016/j.bmcl.2013.08.113. Epub 2013 Sep 7.

Authors

Walter A Henne¹, Sumith A Kularatne, John Hakenjos, Joshua D Carron, Kristene L Henne

Affiliation

¹ Division of Science, Governors State University, 1 University Parkway, University Park, IL 60484, USA. Electronic address: whenne@govst.edu.

PMID: 24064501
DOI: 10.1016/j.bmcl.2013.08.113

Abstract

A folate targeted camptothecin small molecule drug conjugate (SMDC) was synthesized using a monodisperse PEG spacer linked to folate via a releasable disulfide carbonate linker. Cell cytotoxicity in human KB cells exhibited an IC50 of 6nM. Importantly, activity of the prodrug was blocked by excess folate, demonstrating receptor-mediated celluar uptake of the PEG conjugate.

Keywords: Camptothecin; Folate conjugate; Monodisperse PEG; PEG; SMDC; Small molecule drug conjugate.

MeSH terms

Antineoplastic Agents, Phytogenic / administration & dosage
Antineoplastic Agents, Phytogenic / chemistry*
Antineoplastic Agents, Phytogenic / pharmacokinetics
Antineoplastic Agents, Phytogenic / pharmacology
Camptothecin / administration & dosage
Camptothecin / analogs & derivatives*
Camptothecin / pharmacokinetics
Camptothecin / pharmacology
Drug Delivery Systems
Folate Receptors, GPI-Anchored / metabolism
Folic Acid / chemistry*
Humans
KB Cells
Neoplasms / drug therapy
Neoplasms / metabolism
Polyethylene Glycols / chemistry*
Prodrugs / administration & dosage
Prodrugs / chemistry*
Prodrugs / pharmacokinetics
Prodrugs / pharmacology

Substances

Antineoplastic Agents, Phytogenic
Folate Receptors, GPI-Anchored
Prodrugs
Polyethylene Glycols
Folic Acid
Camptothecin