Bioimaging of Nucleolin Aptamer-Containing 5-(N-benzylcarboxyamide)-2′-deoxyuridine More Capable of Specific Binding to Targets in Cancer Cells

Chemically modified nucleotides have been developed and applied into SELEX procedure to find a novel type of aptamers to fit with targets of interest. In this study, we directly performed chemical modification of 5-(N-benzylcarboxyamide)-2′-deoxyuridine (called 5-BzdU) in the AS1411 aptamer, which b...

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Veröffentlicht in:BioMed research international 2010-01, Vol.2010 (2010), p.1-9
Hauptverfasser: Ryu, Sung Ho, Lee, Kyue Yim, Kim, Soonhag, Lee, Jung Hwan, Lee, Dong Soo, Kang, Hyungu
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creator Ryu, Sung Ho
Lee, Kyue Yim
Kim, Soonhag
Lee, Jung Hwan
Lee, Dong Soo
Kang, Hyungu
description Chemically modified nucleotides have been developed and applied into SELEX procedure to find a novel type of aptamers to fit with targets of interest. In this study, we directly performed chemical modification of 5-(N-benzylcarboxyamide)-2′-deoxyuridine (called 5-BzdU) in the AS1411 aptamer, which binds to the nucleolin protein expressed in cancer cells. Forty-seven compounds of AS1411-containing Cy3-labeled 5-BzdU (called Cy3-(5-BzdU)-modified-AS1411) were synthesized by randomly substituting thymidines one to twelve in AS1411 with Cy3-labeled 5-BzdU. Both statistically quantified fluorescence measurements and confocal imaging analysis demonstrated at least three potential compounds of interest: number 12, 29 and 41 that significantly increased the targeting affinity to cancer cells but no significant activity from normal healthy cells. These results suggest that the position and number of substituents in AS1411 are critical parameters to improve the aptamer function. In this study, we demonstrated that chemical modification of the existing aptamers enhanced the binding and targeting affinity to targets of interest without additional SELEX procedures.
doi_str_mv 10.1155/2010/168306
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subjects Animals
Aptamers, Nucleotide - chemistry
Aptamers, Nucleotide - therapeutic use
Biological and medical sciences
Cancer therapies
Cell Line, Tumor
Cervical cancer
CHO Cells
Cricetinae
Cricetulus
Deoxyribonucleic acid
Deoxyuridine - analogs & derivatives
Deoxyuridine - chemistry
DNA
Drug Delivery Systems - methods
HeLa Cells
Humans
Incorporation
Medical sciences
Microscopy, Confocal
Microscopy, Fluorescence
Molecular weight
Neoplasms - chemistry
Neoplasms - drug therapy
Neoplasms - metabolism
Nucleolin
Oligodeoxyribonucleotides - chemistry
Pharmacology. Drug treatments
Phosphoproteins - chemistry
Protein Binding
Rats
RNA-Binding Proteins - chemistry
SELEX Aptamer Technique - methods
title Bioimaging of Nucleolin Aptamer-Containing 5-(N-benzylcarboxyamide)-2′-deoxyuridine More Capable of Specific Binding to Targets in Cancer Cells
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