Synthesis and characterization of oligonucleotides containing conformationally constrained bicyclo[3.1.0]hexane pseudosugar analogs

Martin A. Maier, Yongseok Choi, Hans Gaus, Joseph J. Barchi, Victor E. Marquez, Muthiah Manoharan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Oligodeoxyribonucleotides containing pseudorotationally locked sites derived from bicyclo[3.1.0]hexane pseudosugars have been synthesized using adenosine, thymidine and abasic versions of North- and South-methanocarba nucleosides. The reaction conditions for coupling and oxidation steps of oligonucleotide synthesis have been investigated and optimized to allow efficient and facile solid-phase synthesis using phosphoramidite chemistry. Our studies demonstrate that the use of iodine for P(III) to P(V) oxidation leads to strand cleavage at the sites where the pseudosugar is North. In contrast, the same cleavage reaction was not observed in the case of South pseudosugars. Iodine oxidation generates a 5′-phosphate oligonucleotide fragment on the resin and releases the North pseudosugar into the solution. This side reaction, which is responsible for the extremely low yields observed for the incorporation of the North pseudosugar analogs, has been studied in detail and can be easily overcome by replacing iodine with t-butylhydroperoxide as oxidant.

Original languageEnglish
Pages (from-to)3642-3650
Number of pages9
JournalNucleic Acids Research
Volume32
Issue number12
DOIs
Publication statusPublished - 2004 Sep 13
Externally publishedYes

Fingerprint

Carbasugars
Oligonucleotides
Iodine
Oxidation
tert-Butylhydroperoxide
Solid-Phase Synthesis Techniques
Oligodeoxyribonucleotides
Nucleosides
Oxidants
Adenosine
Thymidine
Resins
Phosphates
bicyclo(3.1.0)hexane

ASJC Scopus subject areas

  • Genetics

Cite this

Synthesis and characterization of oligonucleotides containing conformationally constrained bicyclo[3.1.0]hexane pseudosugar analogs. / Maier, Martin A.; Choi, Yongseok; Gaus, Hans; Barchi, Joseph J.; Marquez, Victor E.; Manoharan, Muthiah.

In: Nucleic Acids Research, Vol. 32, No. 12, 13.09.2004, p. 3642-3650.

Research output: Contribution to journalArticle

Maier, Martin A. ; Choi, Yongseok ; Gaus, Hans ; Barchi, Joseph J. ; Marquez, Victor E. ; Manoharan, Muthiah. / Synthesis and characterization of oligonucleotides containing conformationally constrained bicyclo[3.1.0]hexane pseudosugar analogs. In: Nucleic Acids Research. 2004 ; Vol. 32, No. 12. pp. 3642-3650.
@article{eb60189848014f47aa7795e37264e9e7,
title = "Synthesis and characterization of oligonucleotides containing conformationally constrained bicyclo[3.1.0]hexane pseudosugar analogs",
abstract = "Oligodeoxyribonucleotides containing pseudorotationally locked sites derived from bicyclo[3.1.0]hexane pseudosugars have been synthesized using adenosine, thymidine and abasic versions of North- and South-methanocarba nucleosides. The reaction conditions for coupling and oxidation steps of oligonucleotide synthesis have been investigated and optimized to allow efficient and facile solid-phase synthesis using phosphoramidite chemistry. Our studies demonstrate that the use of iodine for P(III) to P(V) oxidation leads to strand cleavage at the sites where the pseudosugar is North. In contrast, the same cleavage reaction was not observed in the case of South pseudosugars. Iodine oxidation generates a 5′-phosphate oligonucleotide fragment on the resin and releases the North pseudosugar into the solution. This side reaction, which is responsible for the extremely low yields observed for the incorporation of the North pseudosugar analogs, has been studied in detail and can be easily overcome by replacing iodine with t-butylhydroperoxide as oxidant.",
author = "Maier, {Martin A.} and Yongseok Choi and Hans Gaus and Barchi, {Joseph J.} and Marquez, {Victor E.} and Muthiah Manoharan",
year = "2004",
month = "9",
day = "13",
doi = "10.1093/nar/gkh667",
language = "English",
volume = "32",
pages = "3642--3650",
journal = "The BMJ",
issn = "0730-6512",
publisher = "Kluwer Academic Publishers",
number = "12",

}

TY - JOUR

T1 - Synthesis and characterization of oligonucleotides containing conformationally constrained bicyclo[3.1.0]hexane pseudosugar analogs

AU - Maier, Martin A.

AU - Choi, Yongseok

AU - Gaus, Hans

AU - Barchi, Joseph J.

AU - Marquez, Victor E.

AU - Manoharan, Muthiah

PY - 2004/9/13

Y1 - 2004/9/13

N2 - Oligodeoxyribonucleotides containing pseudorotationally locked sites derived from bicyclo[3.1.0]hexane pseudosugars have been synthesized using adenosine, thymidine and abasic versions of North- and South-methanocarba nucleosides. The reaction conditions for coupling and oxidation steps of oligonucleotide synthesis have been investigated and optimized to allow efficient and facile solid-phase synthesis using phosphoramidite chemistry. Our studies demonstrate that the use of iodine for P(III) to P(V) oxidation leads to strand cleavage at the sites where the pseudosugar is North. In contrast, the same cleavage reaction was not observed in the case of South pseudosugars. Iodine oxidation generates a 5′-phosphate oligonucleotide fragment on the resin and releases the North pseudosugar into the solution. This side reaction, which is responsible for the extremely low yields observed for the incorporation of the North pseudosugar analogs, has been studied in detail and can be easily overcome by replacing iodine with t-butylhydroperoxide as oxidant.

AB - Oligodeoxyribonucleotides containing pseudorotationally locked sites derived from bicyclo[3.1.0]hexane pseudosugars have been synthesized using adenosine, thymidine and abasic versions of North- and South-methanocarba nucleosides. The reaction conditions for coupling and oxidation steps of oligonucleotide synthesis have been investigated and optimized to allow efficient and facile solid-phase synthesis using phosphoramidite chemistry. Our studies demonstrate that the use of iodine for P(III) to P(V) oxidation leads to strand cleavage at the sites where the pseudosugar is North. In contrast, the same cleavage reaction was not observed in the case of South pseudosugars. Iodine oxidation generates a 5′-phosphate oligonucleotide fragment on the resin and releases the North pseudosugar into the solution. This side reaction, which is responsible for the extremely low yields observed for the incorporation of the North pseudosugar analogs, has been studied in detail and can be easily overcome by replacing iodine with t-butylhydroperoxide as oxidant.

UR - http://www.scopus.com/inward/record.url?scp=3142752526&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3142752526&partnerID=8YFLogxK

U2 - 10.1093/nar/gkh667

DO - 10.1093/nar/gkh667

M3 - Article

VL - 32

SP - 3642

EP - 3650

JO - The BMJ

JF - The BMJ

SN - 0730-6512

IS - 12

ER -