Thermodynamics of bisphosphonates binding to human bone: A two-site model

Sujoy Mukherjee, Cancan Huang, Francisco Guerra, Ke Wang, Eric Oldfield

Research output: Contribution to journalArticlepeer-review

Abstract

(Figure Presented) We have used isothermal titration calorimetry (ITC) to study the thermodynamics of binding of 12 bisphosphonates to human bone. The ITC results show that there are two binding sites. Site A is the weak, highly populated site seen by NMR and is characterized by an average ΔG of binding of -5.2 kcal. Site B is a strong binding site characterized by a ΔG of binding of -8.5 kcal. Binding to both sites is overwhelmingly entropy driven. Using a thermodynamic group approach and a linear regression method, we predict the ΔG of binding of all 12 compounds with an R 2 = 0.95 (a 0.19 kcal error variance estimate, ∼3% of the total ΔG range), opening up the way to designing novel chemotherapy, immunotherapy, and anti-infectious disease drugs having weak bone binding affinity.

Original languageEnglish (US)
Pages (from-to)8374-8375
Number of pages2
JournalJournal of the American Chemical Society
Volume131
Issue number24
DOIs
StatePublished - Jun 24 2009

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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