Synthesis and evaluation of a conformationally constrained pyridazinone PNA-monomer for recognition of thymine in triple-helix structures

Anne Goldbech Olsen; Otto Dahl; Peter E. Nielsen

doi:10.1016/j.bmcl.2003.12.093

Synthesis and evaluation of a conformationally constrained pyridazinone PNA-monomer for recognition of thymine in triple-helix structures

Anne Goldbech Olsen, Otto Dahl, Peter E. Nielsen

Transcription, RNA, and Gene Medicine Program

Abstract

A novel conformationally constrained pyridazinone E(ag)-base PNA-monomer 2 capable of binding thymine in a triplex motif was designed and synthesised. A bis-PNA with the E(ag)-base incorporated in the Hoogsteen strand was hybridised with a complementary DNA. Thermal stability studies revealed an increase in T(m) (4.3 degrees C per mod.) compared to a no-base unit, but showed no improvement over a previously described unconstrained analogue (E, 1). Surprisingly, no significant difference was found in the thermodynamic parameters (DeltaH degrees, DeltaS degrees and DeltaG degrees ) for PNA-DNA triplex formation involving 2 or the unconstrained analogue 1.

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry Letters
Vol/bind	14
Udgave nummer	6
Sider (fra-til)	1551-4
Antal sider	4
ISSN	0960-894X
DOI	https://doi.org/10.1016/j.bmcl.2003.12.093
Status	Udgivet - 22 mar. 2004

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10.1016/j.bmcl.2003.12.093

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title = "Synthesis and evaluation of a conformationally constrained pyridazinone PNA-monomer for recognition of thymine in triple-helix structures",

abstract = "A novel conformationally constrained pyridazinone E(ag)-base PNA-monomer 2 capable of binding thymine in a triplex motif was designed and synthesised. A bis-PNA with the E(ag)-base incorporated in the Hoogsteen strand was hybridised with a complementary DNA. Thermal stability studies revealed an increase in T(m) (4.3 degrees C per mod.) compared to a no-base unit, but showed no improvement over a previously described unconstrained analogue (E, 1). Surprisingly, no significant difference was found in the thermodynamic parameters (DeltaH degrees, DeltaS degrees and DeltaG degrees ) for PNA-DNA triplex formation involving 2 or the unconstrained analogue 1.",

keywords = "Drug Evaluation, Preclinical/methods, Molecular Structure, Nucleic Acid Conformation, Peptide Nucleic Acids/chemistry, Pyridazines/chemistry, Thermodynamics, Thymine/chemistry",

author = "Olsen, {Anne Goldbech} and Otto Dahl and Nielsen, {Peter E.}",

year = "2004",

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T1 - Synthesis and evaluation of a conformationally constrained pyridazinone PNA-monomer for recognition of thymine in triple-helix structures

AU - Olsen, Anne Goldbech

AU - Dahl, Otto

AU - Nielsen, Peter E.

PY - 2004/3/22

Y1 - 2004/3/22

N2 - A novel conformationally constrained pyridazinone E(ag)-base PNA-monomer 2 capable of binding thymine in a triplex motif was designed and synthesised. A bis-PNA with the E(ag)-base incorporated in the Hoogsteen strand was hybridised with a complementary DNA. Thermal stability studies revealed an increase in T(m) (4.3 degrees C per mod.) compared to a no-base unit, but showed no improvement over a previously described unconstrained analogue (E, 1). Surprisingly, no significant difference was found in the thermodynamic parameters (DeltaH degrees, DeltaS degrees and DeltaG degrees ) for PNA-DNA triplex formation involving 2 or the unconstrained analogue 1.

AB - A novel conformationally constrained pyridazinone E(ag)-base PNA-monomer 2 capable of binding thymine in a triplex motif was designed and synthesised. A bis-PNA with the E(ag)-base incorporated in the Hoogsteen strand was hybridised with a complementary DNA. Thermal stability studies revealed an increase in T(m) (4.3 degrees C per mod.) compared to a no-base unit, but showed no improvement over a previously described unconstrained analogue (E, 1). Surprisingly, no significant difference was found in the thermodynamic parameters (DeltaH degrees, DeltaS degrees and DeltaG degrees ) for PNA-DNA triplex formation involving 2 or the unconstrained analogue 1.

KW - Drug Evaluation, Preclinical/methods

KW - Molecular Structure

KW - Nucleic Acid Conformation

KW - Peptide Nucleic Acids/chemistry

KW - Pyridazines/chemistry

KW - Thermodynamics

KW - Thymine/chemistry

U2 - 10.1016/j.bmcl.2003.12.093

DO - 10.1016/j.bmcl.2003.12.093

M3 - Journal article

C2 - 15006401

SN - 0960-894X

VL - 14

SP - 1551

EP - 1554

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 6

ER -

Synthesis and evaluation of a conformationally constrained pyridazinone PNA-monomer for recognition of thymine in triple-helix structures

Abstract

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