title: Natural-like replication of an unnatural base pair for the expansion of the genetic alphabet and biotechnology applications.
abstract: We synthesized a panel of unnatural base pairs whose pairing depends on hydrophobic and packing forces and identify dTPT3-dNaM, which is PCR amplified with a natural base pair-like efficiency and fidelity. In addition, the dTPT3 scaffold is uniquely tolerant of attaching a propargyl amine linker, resulting in the dTPT3(PA)-dNaM pair, which is amplified only slightly less well. The identification of dTPT3 represents significant progress toward developing an unnatural base pair for the in vivo expansion of an organism's genetic alphabet and for a variety of in vitro biotechnology applications where it is used to site-specifically label amplified DNA, and it also demonstrates for the first time that hydrophobic and packing forces are sufficient to mediate natural-like replication.
authors.affiliation: Department of Chemistry and ‡Center for Protein and Nucleic Acid Research, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Li
authors.forename: Mélissa
authors.initials: M
authors.lastname: Degardin
authors.forename: Thomas
authors.initials: T
authors.lastname: Lavergne
authors.forename: Denis A
authors.initials: DA
authors.lastname: Malyshev
authors.forename: Kirandeep
authors.initials: K
authors.lastname: Dhami
authors.forename: Phillip
authors.initials: P
authors.lastname: Ordoukhanian
authors.forename: Floyd E
authors.initials: FE
authors.lastname: Romesberg
mesh_terms: D020029:Base Pairing; D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D001709:Biotechnology / Q000379:methods*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D016133:Polymerase Chain Reaction / Q000379:methods*