Molecular Mechanism of Proflavine Intercalation: Evidence for Drug-Induced Minimum Base-Stacking Penalty Pathway

Molecular mechanical studies of proflavine and acridine orange intercalation.

Previous workers have reported that proflavine and acridine orange form various structurally different complexes with the dinucleoside phosphates rCpG and dCpG, with uniform C3'-endo and mixed C3'-endo (3'-5') C2'-endo sugar puckers being observed. We present theoretical calculations, based on the method of molecular mechanics, which support the experimental observations. The results suggest th...

Evidence for the intercalation of thalidomide into DNA: clue to the molecular mechanism of thalidomide teratogenicity?

The intercalation of thalidomide (alpha-phthalimidoglutarimide) into nucleic acids was studied by spectrophotometric titrations, displacement of known intercalators, viscosity changes of DNA solutions, and by phase partition analysis. Specific binding of thalidomide was found to DNA of various specimens (human placenta, calf thymus, salmon sperm), but not to RNA (from bakers yeast, torula yeast).

Motifs in nucleic acids: Molecular mechanics restraints for base pairing and base stacking

In building and refining nucleic acid structures, it is often desirable to enforce particular base pairing and/or base stacking interactions. Energy-based modeling programs with classical molecular mechanics force fields do not lend themselves to the easy imposition of penalty terms corresponding to such restraints, because the requirement that two bases lie in or near the same plane (pairing) ...

molecular mechanism of isoniazid-induced mitochondrial toxicity

DNA intercalation optimized by two-step molecular lock mechanism

The diverse properties of DNA intercalators, varying in affinity and kinetics over several orders of magnitude, provide a wide range of applications for DNA-ligand assemblies. Unconventional intercalation mechanisms may exhibit high affinity and slow kinetics, properties desired for potential therapeutics. We used single-molecule force spectroscopy to probe the free energy landscape for an unco...