title: Site-specifically arraying small molecules or proteins on DNA using an expanded genetic alphabet.
abstract: A class of replicable unnatural DNA base pairs formed between d5SICS and either dMMO2, dDMO, or dNaM were developed. To explore the use of these pairs to produce site-specifically labeled DNA, the synthesis of a variety of derivatives bearing propynyl groups, an analysis of their polymerase-mediated replication, and subsequent site-specific modification of the amplified DNA by Click chemistry is reported. With the d5SICS scaffold a propynyl ether linker is accommodated better than its aliphatic analogue, but not as well as the protected propargyl amine linker explored previously. It was also found that with the dMMO2 and dDMO analogues, the dMMO2 position para to the glycosidic linkage is best suited for linker attachment and that although aliphatic and ether-based linkers are similarly accommodated, the direct attachment of an ethynyl group to the nucleobase core is most well tolerated. To demonstrate the utility of these analogues, a variety of them were used to site-selectively attach a biotin tag to the amplified DNA. Finally, we use d5SICS(CO) -dNaM to couple one or two proteins to amplified DNA, with the double labeled product visualized by atomic force microscopy. The ability to encode the spatial relationships of arrayed molecules in PCR amplifiable DNA should have important applications, ranging from SELEX with functionalities not naturally present in DNA to the production, and perhaps "evolution" of nanomaterials.
authors.affiliation: Department of Chemistry and Dr. P. Ordoukhanian Center for Protein and Nucleic Acid Research The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Chemistry and Dr. P. Ordoukhanian Center for Protein and Nucleic Acid Research The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lavergne
authors.affiliation: Department of Chemistry and Dr. P. Ordoukhanian Center for Protein and Nucleic Acid Research The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037.
authors.forename: Denis A
authors.initials: DA
authors.lastname: Malyshev
authors.affiliation: Department of Chemistry and Dr. P. Ordoukhanian Center for Protein and Nucleic Acid Research The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037.
authors.forename: Jörg
authors.initials: J
authors.lastname: Zimmermann
authors.affiliation: Department of Chemistry and Dr. P. Ordoukhanian Center for Protein and Nucleic Acid Research The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037.
authors.forename: Ramkrishna
authors.initials: R
authors.lastname: Adhikary
authors.affiliation: Department of Chemistry and Dr. P. Ordoukhanian Center for Protein and Nucleic Acid Research The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037.
authors.forename: Kirandeep
authors.initials: K
authors.lastname: Dhami
authors.affiliation: Department of Chemistry and Dr. P. Ordoukhanian Center for Protein and Nucleic Acid Research The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037.
authors.forename: Phillip
authors.initials: P
authors.lastname: Ordoukhanian
authors.affiliation: Department of Electrical and Computer Engineering 9500 Gilman Drive University of California, San Diego La Jolla, CA 92093.
authors.forename: Zhelin
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Electrical and Computer Engineering 9500 Gilman Drive University of California, San Diego La Jolla, CA 92093.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Chemistry and Dr. P. Ordoukhanian Center for Protein and Nucleic Acid Research The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037.
authors.forename: Floyd E
authors.initials: FE
authors.lastname: Romesberg
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D004261:DNA Replication; D005815:Genetic Code; D057927:Hydrophobic and Hydrophilic Interactions; D049329:Nanostructures / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry*; D016133:Polymerase Chain Reaction
chemical_list: D009711:Nucleotides; D004247:DNA
keywords: DNA replication; bioconjugation; nanomaterial; nucleic acids; unnatural base pair
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