title: Calorimetric and spectroscopic investigations of the binding of metallated porphyrins to G-quadruplex DNA.
abstract: BACKGROUND
  The human telomere contains tandem repeat of (TTAGG) capable of forming a higher order DNA structure known as G-quadruplex. Porphyrin molecules such as TMPyP4 bind and stabilize G-quadruplex structure.
  
  
  METHODS
  Isothermal titration calorimetry (ITC), circular dichroism (CD), and mass spectroscopy (ESI/MS), were used to investigate the interactions between TMPyP4 and the Co(III), Ni(II), Cu(II), and Zn(II) complexes of TMPyP4 (e.g. Co(III)-TMPyP4) and a model human telomere G-quadruplex (hTel22) at or near physiologic ionic strength ([Na(+)] or [K(+)]≈0.15M).
  
  
  RESULTS
  The apo-TMPyP4, Ni(II)-TMPyP4, and Cu(II)-TMPyP4 all formed complexes having a saturation stoichiometry of 4:1, moles of ligand per mole of DNA. Binding of apo-TMPyP4, Ni(II)-TMPyP4, and Cu(II)-TMPyP4 is described by a "four-independent-sites model". The two highest-affinity sites exhibit a K in the range of 10(8) to 10(10)M(-1) with the two lower-affinity sites exhibiting a K in the range of 10(4) to 10(5)M(-1). Binding of Co(III)-TMPyP4, and Zn(II)-TMPyP4, is best described by a "two-independent-sites model" in which only the end-stacking binding mode is observed with a K in the range of 10(4) to 10(5)M(-1).
  
  
  CONCLUSIONS
  In the case of apo-TMPyP4, Ni(II)-TMPyP4, and Cu(II)-TMPyP4, the thermodynamic signatures for the two binding modes are consistent with an "end stacking" mechanism for the higher affinity binding mode and an "intercalation" mechanism for the lower affinity binding mode. In the case of Co(III)-TMPyP4 and Zn(II)-TMPyP4, both the lower affinity for the "end-stacking" mode and the loss of the intercalative mode for forming the 2:1 complexes with hTel22 are attributed to the preferred metal coordination geometry and the presence of axial ligands.
  
  
  CONCLUSIONS
  The preferred coordination geometry around the metal center strongly influences the energetics of the interactions between the metallated-TMPyP4 and the model human telomeric G-quadruplex.
authors.affiliation: Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, United States.
authors.forename: Jesse I
authors.initials: JI
authors.lastname: DuPont
authors.affiliation: Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, United States.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Henderson
authors.affiliation: Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Metz
authors.affiliation: Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, United States.
authors.forename: Vu H
authors.initials: VH
authors.lastname: Le
authors.affiliation: Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, United States.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Emerson
authors.affiliation: Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, United States.
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Lewis
mesh_terms: D001665:Binding Sites; D002151:Calorimetry; D002413:Cations, Divalent; D002942:Circular Dichroism; D003035:Cobalt / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D007700:Kinetics; D008024:Ligands; D009532:Nickel / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*; D016615:Telomere / Q000737:chemistry; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry*
chemical_list: D002413:Cations, Divalent; D008024:Ligands; D009841:Oligonucleotides; D011166:Porphyrins; C021096:tetra(4-N-methylpyridyl)porphine; D003035:Cobalt; D003300:Copper; D009532:Nickel; D015032:Zinc
keywords: G-quadruplex; Isothermal titration calorimetry; TMPyP4; Telomere; Thermodynamics; hTel22