Thermodynamics of Bisphosphonates Binding to Human Bone: A Two-Site Model
- 2 June 2009
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 131 (24), 8374-8375
- https://doi.org/10.1021/ja902895p
Abstract
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 R2 = 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.This publication has 13 references indexed in Scilit:
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