Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA

K L Dueholm; O Buchardt; J Coull; Peter E. Nielsen

Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA

K L Dueholm, O Buchardt, J Coull, Peter E. Nielsen

Transcription, RNA, and Gene Medicine Program

Abstract

The synthesis and DNA binding properties of bis-PNA (peptide nucleic acid) are reported. Two PNA segments each of seven nucleobases in length were connected in a continuous synthesis via a flexible linker composed of three 8-amino-3,6-dioxaoctanoic acid units. The sequence of the first strand was TCTCTTT (C- to N-terminal), while the second strand was TTTCTCT or TTTJTJT, where J is pseudoisocytosine. These bis-PNAs form triple-stranded complexes of somewhat higher thermal stability than monomeric PNA with complementary oligonucleotides and the thermal melting transition shows very little hysteresis. When the J base is placed in the strand parallel to the DNA complement ('Hoogsteen strand'), the DNA binding was pH independent. The bis-PNAs were also superior to monomeric PNAs for targeting double-stranded DNA by strand invasion.

Original language	English
Journal	Nucleic Acids Research
Volume	23
Issue number	2
Pages (from-to)	217-22
Number of pages	6
ISSN	0305-1048
Publication status	Published - 25 Jan 1995

Keywords

Base Sequence
Binding Sites
Cytosine/analogs & derivatives
DNA/metabolism
Drug Stability
Hot Temperature
Hydrogen-Ion Concentration
Macromolecular Substances
Molecular Sequence Data
Molecular Structure
Potassium Permanganate
Structure-Activity Relationship

Cite this

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title = "Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA",

abstract = "The synthesis and DNA binding properties of bis-PNA (peptide nucleic acid) are reported. Two PNA segments each of seven nucleobases in length were connected in a continuous synthesis via a flexible linker composed of three 8-amino-3,6-dioxaoctanoic acid units. The sequence of the first strand was TCTCTTT (C- to N-terminal), while the second strand was TTTCTCT or TTTJTJT, where J is pseudoisocytosine. These bis-PNAs form triple-stranded complexes of somewhat higher thermal stability than monomeric PNA with complementary oligonucleotides and the thermal melting transition shows very little hysteresis. When the J base is placed in the strand parallel to the DNA complement ('Hoogsteen strand'), the DNA binding was pH independent. The bis-PNAs were also superior to monomeric PNAs for targeting double-stranded DNA by strand invasion.",

keywords = "Base Sequence, Binding Sites, Cytosine/analogs & derivatives, DNA/metabolism, Drug Stability, Hot Temperature, Hydrogen-Ion Concentration, Macromolecular Substances, Molecular Sequence Data, Molecular Structure, Potassium Permanganate, Structure-Activity Relationship",

author = "Dueholm, {K L} and O Buchardt and J Coull and Nielsen, {Peter E.}",

year = "1995",

month = jan,

day = "25",

language = "English",

volume = "23",

pages = "217--22",

journal = "Nucleic Acids Research",

issn = "0305-1048",

publisher = "Oxford University Press",

number = "2",

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TY - JOUR

T1 - Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA

AU - Dueholm, K L

AU - Buchardt, O

AU - Coull, J

AU - Nielsen, Peter E.

PY - 1995/1/25

Y1 - 1995/1/25

N2 - The synthesis and DNA binding properties of bis-PNA (peptide nucleic acid) are reported. Two PNA segments each of seven nucleobases in length were connected in a continuous synthesis via a flexible linker composed of three 8-amino-3,6-dioxaoctanoic acid units. The sequence of the first strand was TCTCTTT (C- to N-terminal), while the second strand was TTTCTCT or TTTJTJT, where J is pseudoisocytosine. These bis-PNAs form triple-stranded complexes of somewhat higher thermal stability than monomeric PNA with complementary oligonucleotides and the thermal melting transition shows very little hysteresis. When the J base is placed in the strand parallel to the DNA complement ('Hoogsteen strand'), the DNA binding was pH independent. The bis-PNAs were also superior to monomeric PNAs for targeting double-stranded DNA by strand invasion.

AB - The synthesis and DNA binding properties of bis-PNA (peptide nucleic acid) are reported. Two PNA segments each of seven nucleobases in length were connected in a continuous synthesis via a flexible linker composed of three 8-amino-3,6-dioxaoctanoic acid units. The sequence of the first strand was TCTCTTT (C- to N-terminal), while the second strand was TTTCTCT or TTTJTJT, where J is pseudoisocytosine. These bis-PNAs form triple-stranded complexes of somewhat higher thermal stability than monomeric PNA with complementary oligonucleotides and the thermal melting transition shows very little hysteresis. When the J base is placed in the strand parallel to the DNA complement ('Hoogsteen strand'), the DNA binding was pH independent. The bis-PNAs were also superior to monomeric PNAs for targeting double-stranded DNA by strand invasion.

KW - Base Sequence

KW - Binding Sites

KW - Cytosine/analogs & derivatives

KW - DNA/metabolism

KW - Drug Stability

KW - Hot Temperature

KW - Hydrogen-Ion Concentration

KW - Macromolecular Substances

KW - Molecular Sequence Data

KW - Molecular Structure

KW - Potassium Permanganate

KW - Structure-Activity Relationship

M3 - Journal article

C2 - 7862524

SN - 0305-1048

VL - 23

SP - 217

EP - 222

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 2

ER -

Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA

Abstract

Keywords

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