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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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. |
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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.</description><identifier>ISSN: 1110-7243</identifier><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 1110-7251</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2010/168306</identifier><identifier>PMID: 20204158</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Puplishing Corporation</publisher><subject>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</subject><ispartof>BioMed research international, 2010-01, Vol.2010 (2010), p.1-9</ispartof><rights>Copyright © 2010</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Kyue Yim Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2010 Kyue Yim Lee et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-c1bdb7c9dec5f35d2ad635711fd8e0c42a1e0418d8739797d6a1788e30e5ad5f3</citedby><cites>FETCH-LOGICAL-c624t-c1bdb7c9dec5f35d2ad635711fd8e0c42a1e0418d8739797d6a1788e30e5ad5f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829770/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829770/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25846600$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20204158$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kang, Daehee</contributor><creatorcontrib>Ryu, Sung Ho</creatorcontrib><creatorcontrib>Lee, Kyue Yim</creatorcontrib><creatorcontrib>Kim, Soonhag</creatorcontrib><creatorcontrib>Lee, Jung Hwan</creatorcontrib><creatorcontrib>Lee, Dong Soo</creatorcontrib><creatorcontrib>Kang, Hyungu</creatorcontrib><title>Bioimaging of Nucleolin Aptamer-Containing 5-(N-benzylcarboxyamide)-2′-deoxyuridine More Capable of Specific Binding to Targets in Cancer Cells</title><title>BioMed research international</title><addtitle>J Biomed Biotechnol</addtitle><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.</description><subject>Animals</subject><subject>Aptamers, Nucleotide - chemistry</subject><subject>Aptamers, Nucleotide - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Cervical cancer</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Deoxyribonucleic acid</subject><subject>Deoxyuridine - analogs & derivatives</subject><subject>Deoxyuridine - chemistry</subject><subject>DNA</subject><subject>Drug Delivery Systems - methods</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Incorporation</subject><subject>Medical sciences</subject><subject>Microscopy, Confocal</subject><subject>Microscopy, Fluorescence</subject><subject>Molecular weight</subject><subject>Neoplasms - chemistry</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - metabolism</subject><subject>Nucleolin</subject><subject>Oligodeoxyribonucleotides - chemistry</subject><subject>Pharmacology. 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Biotechnol</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>2010</volume><issue>2010</issue><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>1110-7243</issn><issn>2314-6133</issn><eissn>1110-7251</eissn><eissn>2314-6141</eissn><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.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Puplishing Corporation</pub><pmid>20204158</pmid><doi>10.1155/2010/168306</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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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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