Recognition of homopyrimidine mismatches by distance-constrained macrocyclic bisintercalators.
Binding of three macrocyclic bisintercalators to mismatch-containing duplexes was analyzed by thermal denaturation experiments, electrospray mass spectrometry studies (ESI-MS) and fluorescent intercalator displacement (FID) titrations. The macrocyclic bisintercalators bind to duplexes containing mismatched thymine bases with high selectivity over the fully matched one and affinity in the submicromolar range (Kd). The FID results also demonstrate that the macrocyclic naphthalene derivative BisNP preferentially binds to pyrimidine-pyrimidine mismatches compared to all other possible base mismatches. This ligand also efficiently competes with a DNA enzyme (M.TaqI) for binding to a duplex with a TT-mismatch.
Bahr
Matthias
M
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52056 Aachen, Germany.
Gabélica
Valerie
V
Granzhan
Anton
A
Weinhold
Elmar
E
Teulade-Fichou
Marie-Paule
MP
D000166:Acridines / Q000737:chemistry*; D020137:Base Pair Mismatch; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D003596:Cytosine / Q000737:chemistry; D004983:Ethanolamines / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry*; D008024:Ligands; D009281:Naphthalenes / Q000737:chemistry*; D013941:Thymine / Q000737:chemistry
D000166:Acridines; C451420:BisA compound; D001952:Bridged-Ring Compounds; D004983:Ethanolamines; D007364:Intercalating Agents; D008024:Ligands; D009281:Naphthalenes; D003596:Cytosine; D013941:Thymine