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

TY - JOUR

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 -