title: Using NMR and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, N8 linked adenosine analog.
abstract: A truly universal nucleobase enables a host of novel applications such as simplified templates for PCR primers, randomized sequencing and DNA based devices. A universal base must pair indiscriminately to each of the canonical bases with little or preferably no destabilization of the overall duplex. In reality, many candidates either destabilize the duplex or do not base pair indiscriminatingly. The novel base 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidin- 4-amine) N8-(2'deoxyribonucleoside), a deoxyadenosine analog (UB), pairs with each of the natural DNA bases with little sequence preference. We have utilized NMR complemented with molecular dynamic calculations to characterize the structure and dynamics of a UB incorporated into a DNA duplex. The UB participates in base stacking with little to no perturbation of the local structure yet forms an unusual base pair that samples multiple conformations. These local dynamics result in the complete disappearance of a single UB proton resonance under native conditions. Accommodation of the UB is additionally stabilized via heightened backbone conformational sampling. NMR combined with various computational techniques has allowed for a comprehensive characterization of both structural and dynamic effects of the UB in a DNA duplex and underlines that the UB as a strong candidate for universal base applications.
authors: Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
authors: Alexander M
authors: AM
authors: Spring-Connell
authors: Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
authors: Marina G
authors: MG
authors: Evich
authors: Laboratorium für Organische und Bioorganische Chemie, Institut für Chemie neuer Materialien, Universität Osnabrück, Barbarastraße 7, 49069 Osnabrück, Germany.
authors: Harald
authors: H
authors: Debelak
authors: Laboratorium für Organische und Bioorganische Chemie, Institut für Chemie neuer Materialien, Universität Osnabrück, Barbarastraße 7, 49069 Osnabrück, Germany Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstraße 11, 48149 Münster, Germany.
authors: Frank
authors: F
authors: Seela
authors: Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA mwg@gsu.edu.
authors: Markus W
authors: MW
authors: Germann
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D006027:Glycosides / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011522:Protons; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D006027:Glycosides; D011522:Protons; C414764:8-aza-7-deazaadenine; D000225:Adenine