Synthesis and activity of a folate peptide camptothecin prodrug

Walter A. Henne; Derek D. Doorneweerd; Andrew R. Hilgenbrink; Sumith A. Kularatne; Philip S. Low

doi:10.1016/j.bmcl.2006.07.076

Synthesis and activity of a folate peptide camptothecin prodrug

Walter A. Henne, Derek D. Doorneweerd, Andrew R. Hilgenbrink, Sumith A. Kularatne, Philip S. Low

Research output: Contribution to journal › Article › peer-review

132 Scopus citations

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 IC₅₀ of 10 nM. Activity of the prodrug was completely blocked by excess folic acid, demonstrating receptor-mediated uptake.

Original language	English (US)
Pages (from-to)	5350-5355
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	20
DOIs	https://doi.org/10.1016/j.bmcl.2006.07.076
State	Published - Oct 15 2006

Keywords

Camptothecin
Carbonate
Disulfide
Endocytosis
Folate
Folic acid
Peptide
Prodrug
Releasable linker
Targeted drug delivery

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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10.1016/j.bmcl.2006.07.076

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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 IC50 of 10 nM. Activity of the prodrug was completely blocked by excess folic acid, demonstrating receptor-mediated uptake.",

keywords = "Camptothecin, Carbonate, Disulfide, Endocytosis, Folate, Folic acid, Peptide, Prodrug, Releasable linker, Targeted drug delivery",

author = "Henne, {Walter A.} and Doorneweerd, {Derek D.} and Hilgenbrink, {Andrew R.} and Kularatne, {Sumith A.} and Low, {Philip S.}",

note = "Funding Information: This work was supported by a Grant from Endocyte Inc. The authors thank Christopher Leamon, Iontcho Vlahov, Marilynn Vetzel, Erina Vlashi, and Karl Wood for their valuable insight. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.bmcl.2006.07.076",

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AU - Henne, Walter A.

AU - Doorneweerd, Derek D.

AU - Hilgenbrink, Andrew R.

AU - Kularatne, Sumith A.

AU - Low, Philip S.

N1 - Funding Information: This work was supported by a Grant from Endocyte Inc. The authors thank Christopher Leamon, Iontcho Vlahov, Marilynn Vetzel, Erina Vlashi, and Karl Wood for their valuable insight. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.

PY - 2006/10/15

Y1 - 2006/10/15

N2 - 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 IC50 of 10 nM. Activity of the prodrug was completely blocked by excess folic acid, demonstrating receptor-mediated uptake.

AB - 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 IC50 of 10 nM. Activity of the prodrug was completely blocked by excess folic acid, demonstrating receptor-mediated uptake.

KW - Camptothecin

KW - Carbonate

KW - Disulfide

KW - Endocytosis

KW - Folate

KW - Folic acid

KW - Peptide

KW - Prodrug

KW - Releasable linker

KW - Targeted drug delivery

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 20

ER -

Synthesis and activity of a folate peptide camptothecin prodrug

Abstract

Keywords

ASJC Scopus subject areas

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