2'-Substituted 2-amino-3-methylpyridine ribonucleosides in triplex-forming oligonucleotides: triplex stability is determined by chemical environment

Chenguang Lou; Qiang Xiao; Radha R. Tailor; Nouha Ben Gaied; Nittaya Gale; Mark E. Light; Keith R. Fox; Tom Brown

doi:10.1039/c1md00068c

2'-Substituted 2-amino-3-methylpyridine ribonucleosides in triplex-forming oligonucleotides: triplex stability is determined by chemical environment

Chenguang Lou, Qiang Xiao, Radha R. Tailor, Nouha Ben Gaied, Nittaya Gale, Mark E. Light, Keith R. Fox, Tom Brown^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

A new synthetic route to the phosphoramidite monomer of 2-amino-3-methyl-5-(2'-O-methyl-beta-D-ribofuranosyl)pyridine (Me-MAP) and its 2'-O-methoxyethyl analogue (MOE-MAP) has been established using D-ribose and 2-amino-3-methyl-5-bromopyridine as precursors. Ultraviolet melting and DNase I footprinting studies indicate that the triplex stabilizing properties of 2'-modified MAPs are determined by the conformation of the entire oligonucleotide backbone. Me-MAP confers a higher triplex stability than 2'-deoxycytidine whereas triplex stabilization by MOE-MAP is similar to that of dC. Incorporation of Me-MAP or MOE-MAP into oligonucleotides renders them dramatically more resistant to degradation by serum nucleases than incorporation of 2-amino-3-methyl-5-(2'-deoxy-beta-D-ribofuranosyl)pyridine (dMAP) or dC.

Original language	English
Pages (from-to)	550-558
Number of pages	9
Journal	MedChemComm
Volume	2
Issue number	6
DOIs	https://doi.org/10.1039/c1md00068c
Publication status	Published - Jun 2011
Externally published	Yes

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title = "2'-Substituted 2-amino-3-methylpyridine ribonucleosides in triplex-forming oligonucleotides: triplex stability is determined by chemical environment",

abstract = "A new synthetic route to the phosphoramidite monomer of 2-amino-3-methyl-5-(2'-O-methyl-beta-D-ribofuranosyl)pyridine (Me-MAP) and its 2'-O-methoxyethyl analogue (MOE-MAP) has been established using D-ribose and 2-amino-3-methyl-5-bromopyridine as precursors. Ultraviolet melting and DNase I footprinting studies indicate that the triplex stabilizing properties of 2'-modified MAPs are determined by the conformation of the entire oligonucleotide backbone. Me-MAP confers a higher triplex stability than 2'-deoxycytidine whereas triplex stabilization by MOE-MAP is similar to that of dC. Incorporation of Me-MAP or MOE-MAP into oligonucleotides renders them dramatically more resistant to degradation by serum nucleases than incorporation of 2-amino-3-methyl-5-(2'-deoxy-beta-D-ribofuranosyl)pyridine (dMAP) or dC.",

author = "Chenguang Lou and Qiang Xiao and Tailor, {Radha R.} and {Ben Gaied}, Nouha and Nittaya Gale and Light, {Mark E.} and Fox, {Keith R.} and Tom Brown",

year = "2011",

month = jun,

doi = "10.1039/c1md00068c",

language = "English",

volume = "2",

pages = "550--558",

journal = "MedChemComm",

issn = "2040-2503",

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T1 - 2'-Substituted 2-amino-3-methylpyridine ribonucleosides in triplex-forming oligonucleotides

T2 - triplex stability is determined by chemical environment

AU - Lou, Chenguang

AU - Xiao, Qiang

AU - Tailor, Radha R.

AU - Ben Gaied, Nouha

AU - Gale, Nittaya

AU - Light, Mark E.

AU - Fox, Keith R.

AU - Brown, Tom

PY - 2011/6

Y1 - 2011/6

N2 - A new synthetic route to the phosphoramidite monomer of 2-amino-3-methyl-5-(2'-O-methyl-beta-D-ribofuranosyl)pyridine (Me-MAP) and its 2'-O-methoxyethyl analogue (MOE-MAP) has been established using D-ribose and 2-amino-3-methyl-5-bromopyridine as precursors. Ultraviolet melting and DNase I footprinting studies indicate that the triplex stabilizing properties of 2'-modified MAPs are determined by the conformation of the entire oligonucleotide backbone. Me-MAP confers a higher triplex stability than 2'-deoxycytidine whereas triplex stabilization by MOE-MAP is similar to that of dC. Incorporation of Me-MAP or MOE-MAP into oligonucleotides renders them dramatically more resistant to degradation by serum nucleases than incorporation of 2-amino-3-methyl-5-(2'-deoxy-beta-D-ribofuranosyl)pyridine (dMAP) or dC.

AB - A new synthetic route to the phosphoramidite monomer of 2-amino-3-methyl-5-(2'-O-methyl-beta-D-ribofuranosyl)pyridine (Me-MAP) and its 2'-O-methoxyethyl analogue (MOE-MAP) has been established using D-ribose and 2-amino-3-methyl-5-bromopyridine as precursors. Ultraviolet melting and DNase I footprinting studies indicate that the triplex stabilizing properties of 2'-modified MAPs are determined by the conformation of the entire oligonucleotide backbone. Me-MAP confers a higher triplex stability than 2'-deoxycytidine whereas triplex stabilization by MOE-MAP is similar to that of dC. Incorporation of Me-MAP or MOE-MAP into oligonucleotides renders them dramatically more resistant to degradation by serum nucleases than incorporation of 2-amino-3-methyl-5-(2'-deoxy-beta-D-ribofuranosyl)pyridine (dMAP) or dC.

U2 - 10.1039/c1md00068c

DO - 10.1039/c1md00068c

M3 - Article

SN - 2040-2503

VL - 2

SP - 550

EP - 558

JO - MedChemComm

JF - MedChemComm

IS - 6

ER -

2'-Substituted 2-amino-3-methylpyridine ribonucleosides in triplex-forming oligonucleotides: triplex stability is determined by chemical environment

Abstract

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