title: Bioimaging of nucleolin aptamer-containing 5-(N-benzylcarboxyamide)-2'-deoxyuridine more capable of specific binding to targets in cancer cells.
abstract: 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.
authors.affiliation: Laboratory of Molecular Imaging, Department of Applied BioScience, CHA Stem Cell Institute, CHA University, Seoul 135-081, South Korea.
authors.forename: Kyue Yim
authors.initials: KY
authors.lastname: Lee
authors.forename: Hyungu
authors.initials: H
authors.lastname: Kang
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Soonhag
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000627:therapeutic use; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry*; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000737:chemistry*; D051381:Rats; D052156:SELEX Aptamer Technique / Q000379:methods*; D000097796:Nucleolin
chemical_list: D052157:Aptamers, Nucleotide; D003857:Deoxyuridine; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C513936:AGRO 100