title: Thermodynamics of bisphosphonates binding to human bone: a two-site model.
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 DeltaG of binding of -5.2 kcal. Site B is a strong binding site characterized by a DeltaG 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 DeltaG of binding of all 12 compounds with an R(2) = 0.95 (a 0.19 kcal error variance estimate, approximately 3% of the total DeltaG range), opening up the way to designing novel chemotherapy, immunotherapy, and anti-infectious disease drugs having weak bone binding affinity.
authors.affiliation: Center for Biophysics & Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Cancan
authors.initials: C
authors.lastname: Huang
authors.forename: Francisco
authors.initials: F
authors.lastname: Guerra
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Eric
authors.initials: E
authors.lastname: Oldfield
mesh_terms: D001842:Bone and Bones / Q000737:chemistry* / Q000378:metabolism; D002151:Calorimetry / Q000379:methods; D004164:Diphosphonates / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008956:Models, Chemical; D013816:Thermodynamics
chemical_list: D004164:Diphosphonates