title: Targeting RNA by small molecules: comparative structural and thermodynamic aspects of aristololactam-β-D-glucoside and daunomycin binding to tRNA(phe).
abstract: BACKGROUND
  Interaction of aristololactam-β-D-glucoside and daunomycin with tRNA(phe) was investigated using various biophysical techniques.
  
  
  RESULTS
  Absorption and fluorescence studies revealed that both the compounds bind tRNA(phe) non-cooperatively. The binding of daunomycin was about one order of magnitude higher than that of aristololactam-β-D-glucoside. Stronger binding of the former was also inferred from fluorescence quenching data, quantum efficiency values and circular dichroic results. Results from isothermal titration calorimetry experiments suggested that the binding of both compounds was predominantly entropy driven with a smaller but favorable enthalpy term that increased with temperature. A large favorable electrostatic contribution to the binding of daunomycin to tRNA(phe) was revealed from salt dependence data and the dissection of the free energy values. The electrostatic component to the free energy change for aristololactam-β-D-glucoside-tRNA(phe) interaction was smaller than that of daunomycin. This was also inferred from the slope of log K versus [Na(+)] plots. Both compounds enhanced the thermal stability of tRNA(phe). The small heat capacity changes of -47 and -99 cal/mol K, respectively, observed for aristololactam-β-D-glucoside and daunomycin, and the observed enthalpy-entropy compensation phenomenon confirmed the involvement of multiple weak noncovalent interactions. Molecular aspects of the interaction have been revealed.
  
  
  CONCLUSIONS
  This study presents the structural and energetic aspects of the binding of aristololactam-β-D-glucoside and daunomycin to tRNA(phe).
authors.affiliation: Biophysical Chemistry Laboratory, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, West Bengal, India.
authors.forename: Abhi
authors.initials: A
authors.lastname: Das
authors.forename: Kakali
authors.initials: K
authors.lastname: Bhadra
authors.forename: Gopinatha
authors.initials: G
authors.lastname: Suresh Kumar
mesh_terms: D000465:Algorithms; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D034341:Aristolochic Acids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D002151:Calorimetry; D002942:Circular Dichroism; D003630:Daunorubicin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D019277:Entropy; D005960:Glucosides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D015394:Molecular Structure; D009690:Nucleic Acid Conformation / Q000187:drug effects; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012360:RNA, Transfer, Phe / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D000903:Antibiotics, Antineoplastic; D034341:Aristolochic Acids; D005960:Glucosides; D012360:RNA, Transfer, Phe; C062008:aristololactam-glucoside; D012313:RNA; D003630:Daunorubicin