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The 2\u2032-\n                    <jats:italic>O<\/jats:italic>\n                    -aminopropyl (AP)-RNA modification displays the highest nuclease resistance among all phosphodiester-based analogues and its RNA binding affinity surpasses that of phosphorothioate DNA by 1\u00b0C per modified residue. We found that oligodeoxynucleotides containing AP-RNA residues at their 3\u2032 ends competitively inhibit the degradation of single-stranded DNA by the\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    Klenow fragment (KF) 3\u2032-5\u2032 exonuclease and snake venom phosphodiesterase. To shed light on the origins of nuclease resistance brought about by the AP modification, we determined the crystal structure of an A-form DNA duplex with AP-RNA modifications at 1.6-\u212b resolution. In addition, the crystal structures of complexes between short DNA fragments carrying AP-RNA modifications and wild-type KF were determined at resolutions between 2.2 and 3.0 \u212b and compared with the structure of the complex between oligo(dT) and the D355A\/E357A KF mutant. The structural models suggest that interference of the positively charged 2\u2032-\n                    <jats:italic>O<\/jats:italic>\n                    -substituent with the metal ion binding site B of the exonuclease allows AP-RNA to effectively slow down degradation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.25.14240","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"14240-14245","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":67,"title":["Structural origins of the exonuclease resistance of a zwitterionic RNA"],"prefix":"10.1073","volume":"96","author":[{"given":"Marianna","family":"Teplova","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Biological Chemistry and The Drug Discovery Program, Northwestern University Medical School, Chicago, IL 60611-3008; Institute of Microbiology and Genetics, University of Vienna, Vienna A-1030, Austria; and Department of Medicinal Chemistry, Isis Pharmaceuticals Inc., Carlsbad, CA 92008"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scot T.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Biological Chemistry and The Drug Discovery Program, Northwestern University Medical School, Chicago, IL 60611-3008; Institute of Microbiology and Genetics, University of Vienna, Vienna A-1030, Austria; and Department of Medicinal Chemistry, Isis Pharmaceuticals Inc., Carlsbad, CA 92008"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Tereshko","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Biological Chemistry and The Drug Discovery Program, Northwestern University Medical School, Chicago, IL 60611-3008; Institute of Microbiology and Genetics, University of Vienna, Vienna A-1030, Austria; and Department of Medicinal Chemistry, Isis Pharmaceuticals Inc., Carlsbad, CA 92008"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Minasov","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Biological Chemistry and The Drug Discovery Program, Northwestern University Medical School, Chicago, IL 60611-3008; Institute of Microbiology and Genetics, University of Vienna, Vienna A-1030, Austria; and Department of Medicinal Chemistry, Isis Pharmaceuticals Inc., Carlsbad, CA 92008"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice M.","family":"Symons","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Biological Chemistry and The Drug Discovery Program, Northwestern University Medical School, Chicago, IL 60611-3008; Institute of Microbiology and Genetics, University of Vienna, Vienna A-1030, Austria; and Department of Medicinal Chemistry, Isis Pharmaceuticals Inc., Carlsbad, CA 92008"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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