7-Deaza-2,8-diazaadenine containing oligonucleotides: synthesis, ring opening and base pairing of 7-halogenated nucleosides

نویسندگان

  • Wenqing Lin
  • Kuiying Xu
  • Frank Seela
  • John A. Montgomery
چکیده

Oligonucleotides containing 7-bromo-7-deaza-2,8-diaza-2 0-deoxyadenosine (3) and 5-amino-3-bromo-4-carbamoyl-1-(2 0deoxy-b-D-erythro-pentofuranosyl)pyrazole (4) were synthesized. Compound 3 was prepared from 7-bromo-8-aza-7-deaza-2 0-deoxyadenosine (5) via the 1,N-etheno derivative 6 and was converted into the phosphoramidite 11. The 7-bromo substituent of 3 increases oligonucleotide duplex stability compared to the non-halogenated nucleoside. Oligonucleotides incorporating 3 are transformed to those containing 4 during long time deprotection at elevated temperature (25% aq ammonia, 60 8C, 30 h). Compound 3 forms a strong base pair with dG. The base pair stability decreases in the order dGOdTOdAOdC. Similar recognition selectivity is observed for the pyrazole nucleoside 4, however, due to decreased stacking and higher flexibility of the pyrazole moiety, duplexes are less stable than those containing 3. q 2005 Elsevier Ltd. All rights reserved.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Pyrazolo[3,4-d][1,2,3]triazine DNA: synthesis and base pairing of 7-deaza-2,8-diaza-2'-deoxyadenosine.

7-deaza-2,8-diaza-2'-deoxyadenosine (4) was synthesized from 8-aza-7-deaza-2'-deoxyadenosine (1) via the 1,N(6)-etheno derivative 5. Ring opening with sodium hydroxide followed by ring closure in the presence of sodium nitrite formed the tricyclic intermediate 5 from which the transiently introduced "etheno" moiety was removed with NBS. Compound 4 was converted to the phosphoramidite 11, which ...

متن کامل

pH-Dependent mismatch discrimination of oligonucleotide duplexes containing 2′-deoxytubercidin and 2- or 7-substituted derivatives: protonated base pairs formed between 7-deazapurines and cytosine

Oligonucleotides incorporating 2'-deoxytubercidin (1a), its 2-amino derivative 2a and related 2-, or 7-substituted analogs (1d, 2b-d, 3 and 4) are synthesized. For this purpose, a series of novel phosphoramidites are prepared and employed in solid-phase synthesis. Hybridization experiments performed with 12mer duplexes indicate that 7-halogenated nucleosides enhance the duplex stability both in...

متن کامل

DNA with stable fluorinated dA and dG substitutes: syntheses, base pairing and 19F-NMR spectra of 7-fluoro-7-deaza-2'-deoxyadenosine and 7-fluoro-7-deaza-2'-deoxyguanosine.

Fluorinated DNA containing stable fluorine substituents in the "purine" base were synthesized for the first time. For this, the phosphoramidites of 7-fluoro-7-deaza-2'-deoxyadenosine and 7-fluoro-7-deaza-2'-deoxyguanosine were prepared and oligonucleotides were synthesized. The 7-fluoro substitution leads to increased duplex stability and more selective base pairing compared to the non-function...

متن کامل

Propynyl groups in duplex DNA: stability of base pairs incorporating 7-substituted 8-aza-7-deazapurines or 5-substituted pyrimidines.

Oligonucleotides incorporating the 7-propynyl derivatives of 8-aza-7-deaza-2'-deoxyguanosine (3b) and 8-aza-7-deaza-2'-deoxyadenosine (4b) were synthesized and their duplex stability was compared with those containing the 5-propynyl derivatives of 2'-deoxycytidine (1) and 2'-deoxyuridine (2). For this purpose phosphoramidites of the 8-aza- 7-deazapurine (pyrazolo[3,4-d]pyrimidine) nucleosides w...

متن کامل

Modification of DNA with octadiynyl side chains: synthesis, base pairing, and formation of fluorescent coumarin dye conjugates of four nucleobases by the alkyne--azide "click" reaction.

Oligonucleotides incorporating 5-(octa-1,7-diynyl)-2'-deoxycytidine 1a, 5-(octa-1,7-diynyl)-2'-deoxyuridine 2a and 7-deaza-7-(octa-1,7-diynyl)-2'-deoxyguanosine 3a, 7-deaza-7-(octa-1,7-diynyl)-2'-deoxyadenosine 4a were prepared. For this, the phosphoramidites 7, 10, and 13 were synthesized and employed in solid-phase oligonucleotide synthesis. The octa-1,7-diynyl nucleosides 1a- 4a were obtaine...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2005