Solid-phase synthesis of positively charged deoxynucleic guanidine (DNG) oligonucleotide incorporating 7-deazaguanine bases.
DNG nucleotides represent a positively charged DNA analog in which the negatively charged phosphodiester linkages of DNA are replaced by positively charged guanidinium linkages. We report herein the synthesis of 3'-end, middle, and 5'-end monomers required for the synthesis of a DNG sequence in which the natural guanine base is replaced by 7-deazaguanine (c(7)G). 7-Deazaguanine nucleobase was chosen because of their unique glycoside bond stability and their ability to prevent G-quartet formation. A facile and high yield two-step synthesis of xylo-7-deazaguanine 7, a key intermediate for introducing 3'-amino functionality, is carried out under Mitsunobu conditions. Subsequently, the 3'-Fmoc-protected thiourea monomers 13 and 19 were prepared from 7 via their corresponding 3'-amino-7-deazaguanines 11 and 18, respectively. The smooth coupling of these thiourea monomers with monomethoxytrityl (MMTr)-protected 3'-end monomer 25, prepared from 5, occurred on solid phase in 3'-->5' direction. The resultant trimeric HO-c(7)Ggc(7)Ggc(7)G-OH (1) has been designed to be included into DNA using standard DNA synthesis technology. The combination of C-c(7)G base pairing and electrostatic association of phosphodiester and guanidinium backbone allows the small synthesized DNG trimer 1 to form 1:1 complex with DNA-C pentamer.
Jain
Moti L
ML
Department of Chemistry and Biochemistry, University Of California, Santa Barbara, 93106, USA.
Bruice
Thomas C
TC
D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
D006146:Guanidines; C088820:deoxynucleic guanidine; D006147:Guanine; D004247:DNA; C066856:7-deazaguanine