Oligonucleotides containing 7-deaza-2 `-deoxyxanthosine: Synthesis, base protection, and base-pair stability

Autor(en): Seela, Frank
Shaikh, Khalil I.
Stichwörter: 2'-DEOXYGUANOSINE; 2'-DEOXYXANTHOSINE; BLOCKING GROUP; Chemistry; Chemistry, Multidisciplinary; DNA; DUPLEXES; GLYCOSYLATION; NITRIC-OXIDE; NUCLEIC-ACIDS; PARALLEL CHAIN ORIENTATION; XANTHINE
Erscheinungsdatum: 2006
Herausgeber: WILEY-V C H VERLAG GMBH
Journal: HELVETICA CHIMICA ACTA
Volumen: 89
Ausgabe: 11
Startseite: 2794
Seitenende: 2814
Zusammenfassung: 
Oligonucleotides incorporating 7-deaza-2'-deoxyxanthosine (3) and 2'-deoxyxanthosine (1) were prepared by solid-phase synthesis using the phosphoramidites 6-9 and 16 which were protected with allyl, diphenylcarbamoyl, or 2-(4-nitrophenyl)ethyl groups. Among the various groups, only the 2-(4-nitrophenyl)ethyl group was applicable to 7-deazaxanthine protection being removed with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) by beta-elimination, while the deprotection of the allyl residue with Pd-0 catalyst or the diphenylcarbamoyl group with ammonia failed. Contrarily, the allyl group was found to be an excellent protecting group for 2'-deoxyxanthosine (1). The base pairing of nucleoside 3 with the four canonical DNA constituents as well as with 3-bromo-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H-pyrazolo[3,4-d]py rimidine-4,6-diamine (4) within the 12-mer duplexes was studied, showing that 7-deaza-2'-deoxyxanthosine (3) has the same universal base-pairing properties as 2'-deoxyxanthosine (1). Contrary to the latter, it is extremely stable at the N-glycosylic bond, while compound 1 is easily hydrolyzed under slightly acidic conditions. Due to the pK(a) values 5.7 (1) and 6.7 (3), both compounds form monoanions under neutral conditions (95% for 1; 65% for 3). Although both compounds form monoanions at pH 7.0, pH-dependent T-m measurements showed that the base-pair stability of 7-deaza-2'-deoxyxanthosine (3) with dT is pH-independent. This indicates that the 2-oxo group is not involved in base-pair formation.
ISSN: 0018019X
DOI: 10.1002/hlca.200690251

Show full item record

Page view(s)

1
Last Week
0
Last month
0
checked on Feb 22, 2024

Google ScholarTM

Check

Altmetric