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Isothermal Titration Calorimetry: A Powerful Tool for the Characterization of Molecular Interactions

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Thermodynamics and Biophysics of Biomedical Nanosystems

Part of the book series: Series in BioEngineering ((SERBIOENG))

Abstract

Isothermal titration calorimetry (ITC) is a well-established technique that allows the accurate and precise determination of binding equilibrium constants. It is able to provide detailed thermodynamic description of reacting systems without the need for van’t Hoff analysis. ITC plays an important role in biology, biochemistry and medicinal chemistry, providing researchers with important information on the structure, stability and functionality of biological and synthetic molecules. This review demonstrates the power and versatility of ITC in providing accurate, rapid, and label-free measurement of the thermodynamics of molecular interactions. Moreover, this work focuses on recent studies employing ITC to investigate compounds of great biotechnological interest.

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References

  1. Berman, H.M., et al.: The protein data bank. Nucleic Acids Res. 28(1), 235–242 (2000)

    Article  MathSciNet  Google Scholar 

  2. Christensen, J.J., Johnston, H.D., Izatt, R.M.: An isothermal titration calorimeter. Rev. Sci. Instrum. 39(9), 1356–1359 (1968)

    Article  Google Scholar 

  3. Wiseman, T., et al.: Rapid measurement of binding constants and heats of binding using a new titration calorimeter. Anal. Biochem. 179(1), 131–137 (1989)

    Article  MathSciNet  Google Scholar 

  4. Horn, J.R., Brandts, J.F., Murphy, K.P.: van’t Hoff and calorimetric enthalpies II: effects of linked equilibria. Biochemistry 41(23), 7501–7507 (2002)

    Article  Google Scholar 

  5. Horn, J.R., et al.: van’t Hoff and calorimetric enthalpies from isothermal titration calorimetry: are there significant discrepancies? Biochemistry 40(6), 1774–1778 (2001)

    Article  Google Scholar 

  6. Kantonen, S.A., Henriksen, N.M., Gilson, M.K.: Accounting for apparent deviations between calorimetric and van’t Hoff enthalpies. Biochim. Biophys. Acta 1862, 692–704 (2018)

    Article  Google Scholar 

  7. Liu, Y., Sturtevant, J.M.: Significant discrepancies between van’t Hoff and calorimetric enthalpies. II. Protein Sci. 4(12), 2559–2561 (1995)

    Article  Google Scholar 

  8. Liu, Y., Sturtevant, J.M.: Significant discrepancies between van’t Hoff and calorimetric enthalpies. III. Biophys. Chem. 64(1–3), 121–126 (1997)

    Article  Google Scholar 

  9. Naghibi, H., Tamura, A., Sturtevant, J.M.: Significant discrepancies between van’t Hoff and calorimetric enthalpies. Proc. Natl. Acad. Sci. U.S.A. 92(12), 5597–5599 (1995)

    Article  Google Scholar 

  10. Turnbull, W.B., Daranas, A.H.: On the value of c: can low affinity systems be studied by isothermal titration calorimetry? J. Am. Chem. Soc. 125(48), 14859–14866 (2003)

    Article  Google Scholar 

  11. Velazquez-Campoy, A., Freire, E.: Isothermal titration calorimetry to determine association constants for high-affinity ligands. Nat. Protoc. 1(1), 186–191 (2006)

    Article  Google Scholar 

  12. Khalifah, R.G., et al.: Thermodynamics of binding of the carbon dioxide-competitive inhibitor imidazole and related compounds to human carbonic anhydrase I: an isothermal titration calorimetry approach to studying weak binding by displacement with strong inhibitors. Biochemistry 32(12), 3058–3066 (1993)

    Article  Google Scholar 

  13. Zhang, Y.L., Zhang, Z.Y.: Low-affinity binding determined by titration calorimetry using a high-affinity coupling ligand: a thermodynamic study of ligand binding to protein tyrosine phosphatase 1B. Anal. Biochem. 261(2), 139–148 (1998)

    Article  Google Scholar 

  14. Sigurskjold, B.W.: Exact analysis of competition ligand binding by displacement isothermal titration calorimetry. Anal. Biochem. 277(2), 260–266 (2000)

    Article  Google Scholar 

  15. Tellinghuisen, J.: Designing isothermal titration calorimetry experiments for the study of 1:1 binding: problems with the “standard protocol”. Anal. Biochem. 424(2), 211–220 (2012)

    Article  Google Scholar 

  16. Nilsson, S.O., Wadso, I.: A flow-microcalorimetric vessel for solution of small quantities of easily or slightly soluble liquids—solution of benzene in water at 298.15-K. J. Chem. Thermodyn. 16(4), 317–330 (1984)

    Google Scholar 

  17. Mizoue, L.S., Tellinghuisen, J.: The role of backlash in the “first injection anomaly” in isothermal titration calorimetry. Anal. Biochem. 326(1), 125–127 (2004)

    Article  Google Scholar 

  18. Markova, N., Hallen, D.: The development of a continuous isothermal titration calorimetric method for equilibrium studies. Anal. Biochem. 331(1), 77–88 (2004)

    Article  Google Scholar 

  19. Christensen, J.J., Hansen, L.D., Izatt, R.M.: Handbook of Proton Ionization Heats and Related Thermodynamic Quantities. Wiley, New York (1976)

    Google Scholar 

  20. Goldberg, R.N., Kishore, N., Lennen, R.M.: Thermodynamic quantities for the ionization reactions of buffers. J. Phys. Chem. Ref. Data 31(2), 231–370 (2002)

    Article  Google Scholar 

  21. de Rivera, M.R., Socorro, F.: Baseline changes in an isothermal titration microcalorimeter. J. Therm. Anal. Calorim. 80(3), 769–773 (2005)

    Article  Google Scholar 

  22. Bhatnagar, R.S., Gordon, J.I.: Thermodynamic studies of myristoyl-coa—protein N-myristoyltransferase using isothermal titration calorimetry. Lipid Modif. Proteins 250, 467–486 (1995)

    Article  Google Scholar 

  23. Brautigam, C.A.: Fitting two- and three-site binding models to isothermal titration calorimetric data. Methods 76, 124–136 (2015)

    Article  Google Scholar 

  24. Brown, A.: Analysis of cooperativity by isothermal titration calorimetry. Int. J. Mol. Sci. 10(8), 3457–3477 (2009)

    Article  Google Scholar 

  25. McPhail, D., Cooper, A.: Thermodynamics and kinetics of dissociation of ligand-induced dimers of vancomycin antibiotics. J. Chem. Soc. Faraday Trans. 93(13), 2283–2289 (1997)

    Article  Google Scholar 

  26. Buurma, N.J., Haq, I.: Advances in the analysis of isothermal titration calorimetry data for ligand-DNA interactions. Methods 42(2), 162–172 (2007)

    Article  Google Scholar 

  27. Keeler, C., et al.: An explicit formulation approach for the analysis of calcium binding to EF-hand proteins using isothermal titration calorimetry. Biophys. J. 105(12), 2843–2853 (2013)

    Article  Google Scholar 

  28. Freire, E., Schon, A., Velazquez-Campoy, A.: Isothermal titration calorimetry: general formalism using binding polynomials. Methods Enzymol. 455, 127–155 (2009)

    Article  Google Scholar 

  29. Ladbury, J.E.: Calorimetry as a tool for understanding biomolecular interactions and an aid to drug design. Biochem. Soc. Trans. 38(4), 888–893 (2010)

    Article  Google Scholar 

  30. Fisher, H.F., Singh, N.: Calorimetric methods for interpreting protein-ligand interactions. Energ. Biol. Macromol. 259, 194–221 (1995)

    Article  Google Scholar 

  31. Ladbury, J.E., Chowdhry, B.Z.: Sensing the heat: the application of isothermal titration calorimetry to thermodynamic studies of biomolecular interactions. Chem. Biol. 3(10), 791–801 (1996)

    Article  Google Scholar 

  32. Livingstone, J.R., Spolar, R.S., Record Jr., M.T.: Contribution to the thermodynamics of protein folding from the reduction in water-accessible nonpolar surface area. Biochemistry 30(17), 4237–4244 (1991)

    Article  Google Scholar 

  33. Spolar, R.S., Livingstone, J.R., Record, M.T.: Use of liquid-hydrocarbon and amide transfer data to estimate contributions to thermodynamic functions of protein folding from the removal of nonpolar and polar surface from water. Biochemistry 31(16), 3947–3955 (1992)

    Article  Google Scholar 

  34. Sturtevant, J.M.: Heat capacity and entropy changes in processes involving proteins. Proc. Natl. Acad. Sci. U.S.A 74(6), 2236–2240 (1977)

    Article  Google Scholar 

  35. Gomez, J., Freire, E.: Thermodynamic mapping of the inhibitor site of the aspartic protease endothiapepsin. J. Mol. Biol. 252(3), 337–350 (1995)

    Article  Google Scholar 

  36. Haq, I., et al.: Specific binding of hoechst 33258 to the d(CGCAAATTTGCG)2 duplex: calorimetric and spectroscopic studies. J. Mol. Biol. 271(2), 244–257 (1997)

    Article  Google Scholar 

  37. Chaires, J.B.: Energetics of drug-DNA interactions. Biopolymers 44(3), 201–215 (1997)

    Article  Google Scholar 

  38. Cooper, A.: Thermodynamic analysis of biomolecular interactions. Curr. Opin. Chem. Biol. 3(5), 557–563 (1999)

    Article  Google Scholar 

  39. Holdgate, G.A., Ward, W.H.: Measurements of binding thermodynamics in drug discovery. Drug Discov. Today 10(22), 1543–1550 (2005)

    Article  Google Scholar 

  40. Spolar, R.S., Record Jr., M.T.: Coupling of local folding to site-specific binding of proteins to DNA. Science 263(5148), 777–784 (1994)

    Article  Google Scholar 

  41. Jeffrey, G.A., Saenger, W.: Hydrogen Bonding in Biological Structures. Springer, New York (1991)

    Google Scholar 

  42. Fersht, A.: Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding, vol. xxi, 631 p. W.H. Freeman, New York (1999)

    Google Scholar 

  43. Scatena, L.F., Brown, M.G., Richmond, G.L.: Water at hydrophobic surfaces: weak hydrogen bonding and strong orientation effects. Science 292(5518), 908–912 (2001)

    Article  Google Scholar 

  44. Matulis, D.: Thermodynamics of the hydrophobic effect. III. Condensation and aggregation of alkanes, alcohols, and alkylamines. Biophys. Chem. 93(1), 67–82 (2001)

    Google Scholar 

  45. Matulis, D., Bloomfield, V.A.: Thermodynamics of the hydrophobic effect. II. Calorimetric measurement of enthalpy, entropy, and heat capacity of aggregation of alkylamines and long aliphatic chains. Biophys. Chem. 93(1), 53–65 (2001)

    Google Scholar 

  46. Matulis, D., Bloomfield, V.A.: Thermodynamics of the hydrophobic effect. I. Coupling of aggregation and pK(a) shifts in solutions of aliphatic amines. Biophys. Chem. 93(1), 37–51 (2001)

    Google Scholar 

  47. Matulis, D., Rouzina, I., Bloomfield, V.A.: Thermodynamics of DNA binding and condensation: isothermal titration calorimetry and electrostatic mechanism. J. Mol. Biol. 296(4), 1053–1063 (2000)

    Article  Google Scholar 

  48. Ahmad, M., et al.: Enthalpy-entropy compensation upon molecular conformational changes. J. Chem. Theory Comput. 11(4), 1410–1418 (2015)

    Article  Google Scholar 

  49. Breiten, B., et al.: Water networks contribute to enthalpy/entropy compensation in protein-ligand binding. J. Am. Chem. Soc. 135(41), 15579–15584 (2013)

    Article  Google Scholar 

  50. Dragan, A.I., Read, C.M., Crane-Robinson, C.: Enthalpy-entropy compensation: the role of solvation. Eur. Biophys. J. 46(4), 301–308 (2017)

    Article  Google Scholar 

  51. Dunitz, J.D.: Win some, lose some: enthalpy-entropy compensation in weak intermolecular interactions. Chem. Biol. 2(11), 709–712 (1995)

    Article  Google Scholar 

  52. Lee, B.: Enthalpy-entropy compensation in the thermodynamics of hydrophobicity. Biophys. Chem. 51(2–3), 271–277; discussion 277–278 (1994)

    Google Scholar 

  53. Holdgate, G.A.: Making cool drugs hot: isothermal titration calorimetry as a tool to study binding energetics. Biotechniques 31(1), 164–166, 168, 170 passim (2001)

    Google Scholar 

  54. Baldwin, R.L.: Temperature dependence of the hydrophobic interaction in protein folding. Proc. Natl. Acad. Sci. U.S.A. 83(21), 8069–8072 (1986)

    Article  Google Scholar 

  55. Privalov, P.L., Gill, S.J.: Stability of protein structure and hydrophobic interaction. Adv. Protein Chem. 39, 191–234 (1988)

    Article  Google Scholar 

  56. Spolar, R.S., Ha, J.H., Record Jr., M.T.: Hydrophobic effect in protein folding and other noncovalent processes involving proteins. Proc. Natl. Acad. Sci. U.S.A. 86(21), 8382–8385 (1989)

    Article  Google Scholar 

  57. Kelley, R.F., O’Connell, M.P.: Thermodynamic analysis of an antibody functional epitope. Biochemistry 32(27), 6828–6835 (1993)

    Article  Google Scholar 

  58. Davies, T.G., Hubbard, R.E., Tame, J.R.: Relating structure to thermodynamics: the crystal structures and binding affinity of eight OppA-peptide complexes. Protein Sci. 8(7), 1432–1444 (1999)

    Article  Google Scholar 

  59. Chaires, J.B.: Calorimetry and thermodynamics in drug design. Ann. Rev. Biophys. 37, 135–151 (2008)

    Article  Google Scholar 

  60. Garbett, N.C., Chaires, J.B.: Thermodynamic studies for drug design and screening. Expert Opin. Drug Discov. 7(4), 299–314 (2012)

    Article  Google Scholar 

  61. Pierce, M.M., Raman, C.S., Nall, B.T.: Isothermal titration calorimetry of protein-protein interactions. Methods 19(2), 213–221 (1999)

    Article  Google Scholar 

  62. Freire, E., Mayorga, O.L., Straume, M.: Isothermal titration calorimetry. Anal. Chem. 62(18), A950–A959 (1990)

    Article  Google Scholar 

  63. Lewis, E.A., Murphy, K.P.: Isothermal titration calorimetry. Methods Mol. Biol. 305, 1–16 (2005)

    Google Scholar 

  64. Leavitt, S., Freire, E.: Direct measurement of protein binding energetics by isothermal titration calorimetry. Curr. Opin. Struct. Biol. 11(5), 560–566 (2001)

    Article  Google Scholar 

  65. Ababou, A., Ladbury, J.E.: Survey of the year 2004: literature on applications of isothermal titration calorimetry. J. Mol. Recognit. 19(1), 79–89 (2006)

    Article  Google Scholar 

  66. Cliff, M.J., Ladbury, J.E.: A survey of the year 2002 literature on applications of isothermal titration calorimetry. J. Mol. Recogn. 16(6), 383–391 (2003)

    Article  Google Scholar 

  67. Ghai, R., Falconer, R.J., Collins, B.M.: Applications of isothermal titration calorimetry in pure and applied research–survey of the literature from 2010. J. Mol. Recogn. 25(1), 32–52 (2012)

    Article  Google Scholar 

  68. Falconer, R.J.: Applications of isothermal titration calorimetry—the research and technical developments from 2011 to 2015. J. Mol. Recogn. 29(10), 504–515 (2016)

    Article  Google Scholar 

  69. Majhi, P.R., Blume, A.: Thermodynamic characterization of temperature-induced micellization and demicellization of detergents studied by differential scanning calorimetry. Langmuir 17(13), 3844–3851 (2001)

    Article  Google Scholar 

  70. Vargas, C., Klingler, J., Keller, S.: Membrane partitioning and translocation studied by isothermal titration calorimetry. Methods Mol. Biol. 1033, 253–271 (2013)

    Article  Google Scholar 

  71. Poncet-Legrand, C., et al.: Interactions between flavan-3-ols and poly(L-proline) studied by isothermal titration calorimetry: effect of the tannin structure. J. Agric. Food Chem. 55(22), 9235–9240 (2007)

    Article  Google Scholar 

  72. Zheng, Y., et al.: Effect of pH on the complexation of kaempferol-4′-glucoside with three beta-cyclodextrin derivatives: isothermal titration calorimetry and spectroscopy study. J. Agric. Food Chem. 62(1), 244–250 (2014)

    Article  Google Scholar 

  73. Baldoni, D., et al.: Performance of microcalorimetry for early detection of methicillin resistance in clinical isolates of Staphylococcus aureus. J. Clin. Microbiol. 47(3), 774–776 (2009)

    Article  Google Scholar 

  74. Xi, L., et al.: Microcalorimetric study of Staphylococcus aureus growth affected by selenium compounds. Thermochim. Acta 387(1), 57–61 (2002)

    Article  MathSciNet  Google Scholar 

  75. Mariana, F., et al.: Isothermal titration calorimetry—a new method for the quantification of microbial degradation of trace pollutants. J. Microbiol. Methods 82(1), 42–48 (2010)

    Article  Google Scholar 

  76. Hansen, L.D., et al.: Enzyme-catalyzed and binding reaction kinetics determined by titration calorimetry. Biochim. Biophys. Acta 1860(5), 957–966 (2016)

    Article  Google Scholar 

  77. Transtrum, M.K., Hansen, L.D., Quinn, C.: Enzyme kinetics determined by single-injection isothermal titration calorimetry. Methods 76, 194–200 (2015)

    Article  Google Scholar 

  78. Demarse, N.A., et al.: Determining enzyme kinetics via isothermal titration calorimetry. Methods Mol. Biol. 978, 21–30 (2013)

    Article  Google Scholar 

  79. Todd, M.J., Gomez, J.: Enzyme kinetics determined using calorimetry: a general assay for enzyme activity? Anal. Biochem. 296(2), 179–187 (2001)

    Article  Google Scholar 

  80. Hughes, J.P., et al.: Principles of early drug discovery. Br. J. Pharmacol. 162(6), 1239–1249 (2011)

    Article  Google Scholar 

  81. Ruben, A.J., Kiso, Y., Freire, E.: Overcoming roadblocks in lead optimization: a thermodynamic perspective. Chem. Biol. Drug Des. 67(1), 2–4 (2006)

    Article  Google Scholar 

  82. Torres, F.E., et al.: Higher throughput calorimetry: opportunities, approaches and challenges. Curr. Opin. Struct. Biol. 20(5), 598–605 (2010)

    Article  Google Scholar 

  83. Zhou, X., Kini, R.M., Sivaraman, J.: Application of isothermal titration calorimetry and column chromatography for identification of biomolecular targets. Nat. Protoc. 6(2), 158–165 (2011)

    Article  Google Scholar 

  84. Malmsten, M.: Soft drug delivery systems. Soft Matter 2(9), 760–769 (2006)

    Article  Google Scholar 

  85. Gwinn, M.R., Vallyathan, V.: Nanoparticles: health effects—pros and cons. Environ. Health Perspect. 114(12), 1818–1825 (2006)

    Article  Google Scholar 

  86. Cedervall, T., et al.: Detailed identification of plasma proteins adsorbed on copolymer nanoparticles. Angew. Chem. Int. Ed. Engl. 46(30), 5754–5756 (2007)

    Article  Google Scholar 

  87. Saptarshi, S.R., Duschl, A., Lopata, A.L.: Interaction of nanoparticles with proteins: relation to bio-reactivity of the nanoparticle. J. Nanobiotechnol. 11, 26 (2013)

    Article  Google Scholar 

  88. Mandal, S., et al.: Interaction of carbon nanoparticles to serum albumin: elucidation of the extent of perturbation of serum albumin conformations and thermodynamical parameters. J. Hazard. Mater. 248–249, 238–245 (2013)

    Article  Google Scholar 

  89. Malmsten, M.: Inorganic nanomaterials as delivery systems for proteins, peptides, DNA, and siRNA. Curr. Opin. Colloid Interface Sci. 18(5), 468–480 (2013)

    Article  Google Scholar 

  90. Cukalevski, R., et al.: Structural changes in apolipoproteins bound to nanoparticles. Langmuir 27(23), 14360–14369 (2011)

    Article  Google Scholar 

  91. Cedervall, T., et al.: Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc. Natl. Acad. Sci. 104(7), 2050–2055 (2007)

    Article  MathSciNet  Google Scholar 

  92. Fleischer, C.C., Payne, C.K.: Secondary structure of corona proteins determines the cell surface receptors used by nanoparticles. J. Phys. Chem. B 118(49), 14017–14026 (2014)

    Article  Google Scholar 

  93. Eren, N.M., Narsimhan, G., Campanella, O.H.: Protein adsorption induced bridging flocculation: the dominant entropic pathway for nano-bio complexation. Nanoscale 8(6), 3326–3336 (2016)

    Article  Google Scholar 

  94. Decher, G., Schlenoff, J.B.: Multilayer thin Films: Sequential Assembly Of Nanocomposite Materials. 2nd compl. rev. and enl. edn. Wiley, Weinheim (2012)

    Google Scholar 

  95. Dan, N.: The structure of DNA complexes with cationic liposomes-cylindrical or flat bilayers? Biochim. Biophys. Acta 1369(1), 34–38 (1998)

    Article  Google Scholar 

  96. Golan, R., et al.: DNA toroids: stages in condensation. Biochemistry 38(42), 14069–14076 (1999)

    Article  Google Scholar 

  97. Vilfan, I.D., et al.: Time study of DNA condensate morphology: implications regarding the nucleation, growth, and equilibrium populations of toroids and rods. Biochemistry 45(26), 8174–8183 (2006)

    Article  Google Scholar 

  98. Perspicace, S., et al.: Isothermal titration calorimetry with micelles: Thermodynamics of inhibitor binding to carnitine palmitoyltransferase 2 membrane protein. FEBS Open Bio 3, 204–211 (2013)

    Article  Google Scholar 

  99. Loh, W., Brinatti, C., Tam, K.C.: Use of isothermal titration calorimetry to study surfactant aggregation in colloidal systems. Biochim. Biophys. Acta 1860(5), 999–1016 (2016)

    Article  Google Scholar 

  100. Marsh, D.: Thermodynamics of phospholipid self-assembly. Biophys. J. 102(5), 1079–1087 (2012)

    Article  Google Scholar 

  101. Feng, X., Leduc, M., Pelton, R.: Polyelectrolyte complex characterization with isothermal titration calorimetry and colloid titration. Colloids Surf. A 317(1), 535–542 (2008)

    Article  Google Scholar 

  102. Maurstad, G., Kitamura, S., Stokke, B.T.: Isothermal titration calorimetry study of the polyelectrolyte complexation of xanthan and chitosan samples of different degree of polymerization. Biopolymers 97(1), 1–10 (2012)

    Article  Google Scholar 

  103. Lounis, F.M., et al.: Interactions between oppositely charged polyelectrolytes by isothermal titration calorimetry: effect of ionic strength and charge density. J. Phys. Chem. B 121(12), 2684–2694 (2017)

    Article  Google Scholar 

  104. Manning, G.S.: Limiting laws and counterion condensation in polyelectrolyte solutions I. Colligative properties. J. Chem. Phys. 51(3), 924–933 (1969)

    Google Scholar 

  105. Sideratou, Z., et al.: Arginine end-functionalized poly(L-lysine) dendrigrafts for the stabilization and controlled release of insulin. J. Colloid Interface Sci. 351(2), 433–441 (2010)

    Article  Google Scholar 

  106. Bulbake, U., et al.: Liposomal formulations in clinical use: an updated review. Pharmaceutics 9(2), 12 (2017)

    Article  Google Scholar 

  107. Sercombe, L., et al.: Advances and challenges of liposome assisted drug delivery. Front Pharmacol 6, 286 (2015)

    Article  Google Scholar 

  108. Ikonen, M., Murtomaki, L., Kontturi, K.: Microcalorimetric and zeta potential study on binding of drugs on liposomes. Colloids Surf B Biointerfaces 78(2), 275–282 (2010)

    Article  Google Scholar 

  109. Al-Kaddah, S., et al.: Analysis of membrane interactions of antibiotic peptides using ITC and biosensor measurements. Biophys. Chem. 152(1), 145–152 (2010)

    Article  Google Scholar 

  110. Allain, V., Bourgaux, C., Couvreur, P.: Self-assembled nucleolipids: from supramolecular structure to soft nucleic acid and drug delivery devices. Nucleic Acids Res. 40(5), 1891–1903 (2012)

    Article  Google Scholar 

  111. Thanassoulas, A., et al.: From nucleobases to nucleolipids: an ITC approach on the thermodynamics of their interactions in aqueous solutions. J. Phys. Chem. B 118(24), 6570–6585 (2014)

    Article  Google Scholar 

  112. Patwa, A., et al.: Tuning molecular interactions in lipid-oligonucleotides assemblies via locked nucleic acid (LNA)-based lipids. Org. Biomol. Chem. 11(41), 7108–7112 (2013)

    Article  Google Scholar 

  113. Lipinski, C.A.: Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods 44(1), 235–249 (2000)

    Article  Google Scholar 

  114. Amidon, G.L., et al.: A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. 12(3), 413–420 (1995)

    Article  Google Scholar 

  115. Gidwani, B., Vyas, A.: A comprehensive review on cyclodextrin-based carriers for delivery of chemotherapeutic cytotoxic anticancer drugs. Biomed. Res. Int. 2015, 198268 (2015)

    Article  Google Scholar 

  116. Villiers, A.: Sur la fermentation de la fécule par l’action du ferment butyrique. Compt. Rend. Acad. Sci 112, 536–538 (1891)

    Google Scholar 

  117. Lipinski, C.A., et al.: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46(1–3), 3–26 (2001)

    Article  Google Scholar 

  118. Marttin, E., Verhoef, J.C., Merkus, F.W.: Efficacy, safety and mechanism of cyclodextrins as absorption enhancers in nasal delivery of peptide and protein drugs. J. Drug Target. 6(1), 17–36 (1998)

    Article  Google Scholar 

  119. Connors, K.A.: The stability of cyclodextrin complexes in solution. Chem. Rev. 97(5), 1325–1358 (1997)

    Article  Google Scholar 

  120. Segura-Sanchez, F., et al.: Elucidation of the complexation mechanism between (+)-usnic acid and cyclodextrins studied by isothermal titration calorimetry and phase-solubility diagram experiments. J. Mol. Recogn. 22(3), 232–241 (2009)

    Article  Google Scholar 

  121. Mazzaferro, S., et al.: Bivalent sequential binding of docetaxel to methyl-beta-cyclodextrin. Int. J. Pharm. 416(1), 171–180 (2011)

    Article  Google Scholar 

  122. Ignaczak, A., Palecz, B., Belica-Pacha, S.: Quantum chemical study and isothermal titration calorimetry of beta-cyclodextrin complexes with mianserin in aqueous solution. Org. Biomol. Chem. 15(5), 1209–1216 (2017)

    Article  Google Scholar 

  123. Agnes, M., et al.: Designed positively charged cyclodextrin hosts with enhanced binding of penicillins as carriers for the delivery of antibiotics: the case of oxacillin. Int. J. Pharm. 531(2), 480–491 (2017)

    Article  Google Scholar 

  124. Nguyen, H.H., et al.: Surface plasmon resonance: a versatile technique for biosensor applications. Sens. (Basel) 15(5), 10481–10510 (2015)

    Article  Google Scholar 

  125. Piliarik, M., Vaisocherova, H., Homola, J.: Surface plasmon resonance biosensing. Methods Mol. Biol. 503, 65–88 (2009)

    Article  Google Scholar 

  126. Tyszka, J.M., Fraser, S.E., Jacobs, R.E.: Magnetic resonance microscopy: recent advances and applications. Curr. Opin. Biotechnol. 16(1), 93–99 (2005)

    Article  Google Scholar 

  127. Cala, O., Guilliere, F., Krimm, I.: NMR-based analysis of protein-ligand interactions. Anal. Bioanal. Chem. 406(4), 943–956 (2014)

    Article  Google Scholar 

  128. Lebowitz, J., Lewis, M.S., Schuck, P.: Modern analytical ultracentrifugation in protein science: a tutorial review. Protein Sci. 11(9), 2067–2079 (2002)

    Article  Google Scholar 

  129. Howlett, G.J., Minton, A.P., Rivas, G.: Analytical ultracentrifugation for the study of protein association and assembly. Curr. Opin. Chem. Biol. 10(5), 430–436 (2006)

    Article  Google Scholar 

  130. Rossi, A.M., Taylor, C.W.: Analysis of protein-ligand interactions by fluorescence polarization. Nat. Protoc. 6(3), 365–387 (2011)

    Article  Google Scholar 

  131. Hall, M.D., et al.: Fluorescence polarization assays in high-throughput screening and drug discovery: a review. Methods Appl. Fluoresci. 4(2), 022001 (2016)

    Article  Google Scholar 

  132. Heegaard, N.H., Nilsson, S., Guzman, N.A.: Affinity capillary electrophoresis: important application areas and some recent developments. J. Chromatogr. B Biomed. Sci. Appl. 715(1), 29–54 (1998)

    Article  Google Scholar 

  133. Albishri, H.M., et al.: Recent advances in affinity capillary electrophoresis for binding studies. Bioanalysis 6(24), 3369–3392 (2014)

    Article  Google Scholar 

  134. Hofstadler, S.A., Sannes-Lowery, K.A.: Applications of ESI-MS in drug discovery: interrogation of noncovalent complexes. Nat. Rev. Drug Discov. 5(7), 585–595 (2006)

    Article  Google Scholar 

  135. Vivat Hannah, V., et al.: Native MS: an ‘ESI’ way to support structure- and fragment-based drug discovery. Future Med. Chem. 2(1), 35–50 (2010)

    Article  Google Scholar 

  136. Freyer, M.W., Lewis, E.A.: Isothermal titration calorimetry: experimental design, data analysis, and probing macromolecule/ligand binding and kinetic interactions. Methods Cell Biol. 84, 79–113 (2008)

    Article  Google Scholar 

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Thanassoulas, A., Nounesis, G. (2019). Isothermal Titration Calorimetry: A Powerful Tool for the Characterization of Molecular Interactions. In: Demetzos, C., Pippa, N. (eds) Thermodynamics and Biophysics of Biomedical Nanosystems. Series in BioEngineering. Springer, Singapore. https://doi.org/10.1007/978-981-13-0989-2_4

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