Synthesis, characterization, and in vitro assay of folic acid conjugates of 3′-azido-3′-deoxythymidine (AZT): Toward targeted AZT based anticancer therapeutics

Anthony R. Vortherms; Robert P. Doyle; Dayuan Gao; Olivia Debrah; Patrick J. Sinko

doi:10.1080/15257770701795946

Synthesis, characterization, and in vitro assay of folic acid conjugates of 3′-azido-3′-deoxythymidine (AZT): Toward targeted AZT based anticancer therapeutics

Anthony R. Vortherms, Robert P. Doyle, Dayuan Gao, Olivia Debrah, Patrick J. Sinko

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

18 Scopus citations

Abstract

Conjugates of three components namely folic acid, poly(ethyleneglycol) and 3 ′-azido-3 ′-deoxythymidine (AZT) are presented. Folate-PEG units were coupled to AZT to facilitate delivery of the nucleoside into the cell. A convenient separation of the polydisperse PEGylated-folic acid regioisomers produced upon conjugation is described. This is to select for the active γ-regioisomer over the inactive α-regioisomer. In vitro cytotoxicity assays were conducted against an ovarian cell line (A2780/AD) that overexpresses the folate receptor (FR) and compared to a FR free control cell line. Compared to AZT a ∼20-fold greater potency against the resistant ovarian line was observed for the conjugates.

Original language	English (US)
Pages (from-to)	173-185
Number of pages	13
Journal	Nucleosides, Nucleotides and Nucleic Acids
Volume	27
Issue number	2
DOIs	https://doi.org/10.1080/15257770701795946
State	Published - Feb 2008

Keywords

3′-azido-3′-deoxythymidine nucleoside
Anticancer agent
Folic acid
Isomer separation

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Genetics

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10.1080/15257770701795946

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Synthesis, characterization, and in vitro assay of folic acid conjugates of 3′-azido-3′-deoxythymidine (AZT): Toward targeted AZT based anticancer therapeutics. / Vortherms, Anthony R.; Doyle, Robert P.; Gao, Dayuan et al.
In: Nucleosides, Nucleotides and Nucleic Acids, Vol. 27, No. 2, 02.2008, p. 173-185.

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

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abstract = "Conjugates of three components namely folic acid, poly(ethyleneglycol) and 3 ′-azido-3 ′-deoxythymidine (AZT) are presented. Folate-PEG units were coupled to AZT to facilitate delivery of the nucleoside into the cell. A convenient separation of the polydisperse PEGylated-folic acid regioisomers produced upon conjugation is described. This is to select for the active γ-regioisomer over the inactive α-regioisomer. In vitro cytotoxicity assays were conducted against an ovarian cell line (A2780/AD) that overexpresses the folate receptor (FR) and compared to a FR free control cell line. Compared to AZT a ∼20-fold greater potency against the resistant ovarian line was observed for the conjugates.",

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AU - Debrah, Olivia

AU - Sinko, Patrick J.

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AB - Conjugates of three components namely folic acid, poly(ethyleneglycol) and 3 ′-azido-3 ′-deoxythymidine (AZT) are presented. Folate-PEG units were coupled to AZT to facilitate delivery of the nucleoside into the cell. A convenient separation of the polydisperse PEGylated-folic acid regioisomers produced upon conjugation is described. This is to select for the active γ-regioisomer over the inactive α-regioisomer. In vitro cytotoxicity assays were conducted against an ovarian cell line (A2780/AD) that overexpresses the folate receptor (FR) and compared to a FR free control cell line. Compared to AZT a ∼20-fold greater potency against the resistant ovarian line was observed for the conjugates.

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KW - Folic acid

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Synthesis, characterization, and in vitro assay of folic acid conjugates of 3′-azido-3′-deoxythymidine (AZT): Toward targeted AZT based anticancer therapeutics

Abstract

Keywords

ASJC Scopus subject areas

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