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. 2015 Feb 21;6(4):397-401.
doi: 10.1021/ml5004603. eCollection 2015 Apr 9.

Structural requirements for bisphosphonate binding on hydroxyapatite: NMR study of bisphosphonate partial esters

Elina Puljula  1 , Petri Turhanen  1 , Jouko Vepsäläinen  1 , Maelle Monteil  2 , Marc Lecouvey  2 , Janne Weisell  1
Affiliations

Structural requirements for bisphosphonate binding on hydroxyapatite: NMR study of bisphosphonate partial esters

Elina Puljula et al. ACS Med Chem Lett. .

Abstract

Eighteen different bisphosphonates, including four clinically used bisphosphonate acids and their phosphoesters, were studied to evaluate how the bisphosphonate structure affects binding to bone. Bisphosphonates with weak bone affinity, such as clodronate, could not bind to hydroxyapatite after the addition of one ester group. Medronate retained its ability to bind after the addition of one ester group, and hydroxy-bisphosphonates could bind even after the addition of two ester groups. Thus, several bisphosphonate esters are clearly bone binding compounds. The following conclusions about bisphosphonate binding emerge: (1) a hydroxyl group in the geminal carbon takes part in the binding process and increases the bisphosphonate's ability to bind to bone; (2) the bisphosphonate's ability to bind decreases when the amount of ester groups increases; and (3) the location of the ester groups affects the bisphosphonate's binding ability.

Keywords: Bisphosphonates; alendronate; etidronate; hydroxyapatite; nuclear magnetic resonance.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Structures of the BP esters and the corresponding BP acids used in this study.
Figure 2
Figure 2
HAP binding of BP acids and their esters. The amount of HAP-bound BP is stated in percentages. It is calculated from the concentration difference between BP solution before and after incubation with HAP.
Figure 3
Figure 3
HAP binding of different BP esters proportioned to the HAP binding of the corresponding BP acid.
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