Targeting DNA Bulged Microenvironments with Synthetic Agents: Lessons from a Natural Product
Bulged regions of nucleic acids are important structural motifs whose function has been linked to a number of key nuclear processes. Additionally, bulged intermediates have been implicated in the etiology of several genetic diseases and as targets for viral regulation. Despite these obvious ramifica...
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| Veröffentlicht in: | Chemistry & biology 2002-08, Vol.9 (8), p.925-931 |
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| creator | Xi, Zhen Hwang, Geum-Sook Goldberg, Irving H Harris, Jeffrey L Pennington, William T Fouad, Farid S Qabaja, Ghassan Wright, Justin M Jones, Graham B |
| description | Bulged regions of nucleic acids are important structural motifs whose function has been linked to a number of key nuclear processes. Additionally, bulged intermediates have been implicated in the etiology of several genetic diseases and as targets for viral regulation. Despite these obvious ramifications, few molecules are capable of selective binding to bulged sequences. Prompted by the remarkable affinity of a natural product metabolite, we have designed and prepared a series of readily accessible synthetic agents with selective bulge binding activity. Furthermore, by screening a library of bulge-containing oligodeoxynucelotides, correlations between structure and affinity of the agents can be drawn. In addition to potential applications in molecular biology, the availability of these spirocyclic agents now opens the door for rational drug design. |
| doi_str_mv | 10.1016/S1074-5521(02)00188-6 |
| format | Article |
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In addition to potential applications in molecular biology, the availability of these spirocyclic agents now opens the door for rational drug design.</description><subject>Antineoplastic Agents - chemistry</subject><subject>Cyclization</subject><subject>DNA - chemistry</subject><subject>DNA - drug effects</subject><subject>DNA - metabolism</subject><subject>Drug Design</subject><subject>Drug Evaluation, Preclinical</subject><subject>Enediynes</subject><subject>Gene Library</subject><subject>Hydrolysis - drug effects</subject><subject>Ligands</subject><subject>Nucleic Acid Conformation - drug effects</subject><subject>Oligodeoxyribonucleotides - chemistry</subject><subject>Oligodeoxyribonucleotides - metabolism</subject><subject>Spiro Compounds - chemical synthesis</subject><subject>Spiro Compounds - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Zinostatin - analogs & derivatives</subject><subject>Zinostatin - chemistry</subject><issn>1074-5521</issn><issn>1879-1301</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkclOHDEQQK0IBAT4BCKfonBoqHJvdi5oIAtIwyTSkBuS1W1XD456IbYbxN-nm-XMqUqlp9oeY0cIJwhYnK4RyizJc4FfQBwDoJRJ8YHtoSxVging1pS_IbvsYwh_YaZUscN2UQjICiX22O1N5TcUXb_h31YLfj62G7L82hk_UP_g_NB31MfAH1284-unPt5NsOGLzVz9ypcUwtAH3vih4xVfVXH0Vct_-8GOJh6w7aZqAx2-xn3258f3m4vLZPnr59XFYpmQUFlMMsqolI2qSzTCNgIzkqBkVteNnLavstTKxiqrZCnzugRrSOQIFtPGIkKT7rPPL33v_fBvpBB154Khtq16GsagSwE5CKXeBXGaV-TFDH56Bce6I6vvvesq_6TfHjcBZy8ATXc9OPI6GEe9Ies8majt4DSCnlXpZ1V69qBB6GdVukj_A2LjhLQ</recordid><startdate>20020801</startdate><enddate>20020801</enddate><creator>Xi, Zhen</creator><creator>Hwang, Geum-Sook</creator><creator>Goldberg, Irving H</creator><creator>Harris, Jeffrey L</creator><creator>Pennington, William T</creator><creator>Fouad, Farid S</creator><creator>Qabaja, Ghassan</creator><creator>Wright, Justin M</creator><creator>Jones, Graham B</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>20020801</creationdate><title>Targeting DNA Bulged Microenvironments with Synthetic Agents: Lessons from a Natural Product</title><author>Xi, Zhen ; 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Additionally, bulged intermediates have been implicated in the etiology of several genetic diseases and as targets for viral regulation. Despite these obvious ramifications, few molecules are capable of selective binding to bulged sequences. Prompted by the remarkable affinity of a natural product metabolite, we have designed and prepared a series of readily accessible synthetic agents with selective bulge binding activity. Furthermore, by screening a library of bulge-containing oligodeoxynucelotides, correlations between structure and affinity of the agents can be drawn. In addition to potential applications in molecular biology, the availability of these spirocyclic agents now opens the door for rational drug design.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>12204692</pmid><doi>10.1016/S1074-5521(02)00188-6</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Antineoplastic Agents - chemistry Cyclization DNA - chemistry DNA - drug effects DNA - metabolism Drug Design Drug Evaluation, Preclinical Enediynes Gene Library Hydrolysis - drug effects Ligands Nucleic Acid Conformation - drug effects Oligodeoxyribonucleotides - chemistry Oligodeoxyribonucleotides - metabolism Spiro Compounds - chemical synthesis Spiro Compounds - pharmacology Structure-Activity Relationship Zinostatin - analogs & derivatives Zinostatin - chemistry |
| title | Targeting DNA Bulged Microenvironments with Synthetic Agents: Lessons from a Natural Product |
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