A di(bisphosphonic acid) for protein coupling and targeting to bone

Journal of Pharmaceutical Sciences
Geeti BansalHasan Uludag

Abstract

Proteins intended for treatment of bone diseases should ideally exhibit a high bone affinity, so that they are preferentially deposited to bones after systemic administration. This can be achieved by combining molecules having a high affinity to bone with the proteins. Bisphosphonates (BPs) are chemical analogs of pyrophosphate that possess exceptional bone mineral affinity. To this end, we synthesized a novel BP, 3,5-di(ethylamino-2,2-bisphosphono)benzoic acid (6), which contains two BP moieties on a single molecule, unlike conventional BPs that contain one BP moiety per molecule. 6 was then conjugated to two model proteins, bovine serum albumin and nonspecific bovine immunoglobulin G by the carbodiimide chemistry. By varying the reagent concentrations, the conjugation efficiency (i.e., number of 6 per protein) was readily controlled under the experimental conditions. The protein-6 conjugates exhibited an in vitro mineral affinity that was proportional to the number of conjugated 6. The 6-conjugates of both bovine serum albumin and immunoglobulin G were found to be bone seeking in rats, based on the increased concentration of 6-conjugated proteins in bone tissue after intravenous administration. We conclude that the novel BP s...Continue Reading

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Citations

Feb 13, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Amal A El-Mabhouh, John R Mercer
Nov 16, 2007·Bioconjugate Chemistry·Robin S EhrickLeonidas G Bachas
Feb 18, 2010·Journal of Drug Targeting·Guilin WangHasan Uludağ
Sep 29, 2011·Journal of Pharmaceutical Sciences·Yunlong ZhengMitsuru Hashida
Jul 23, 2005·Journal of Biomedical Materials Research. Part a·Geeti BansalHasan Uludag
Oct 21, 2015·Advanced Drug Delivery Reviews·Lisa E ColeRyan K Roeder
Nov 22, 2005·Expert Opinion on Drug Delivery·Mathew VarkeyHasan Uludag
Feb 28, 2007·Chemical Society Reviews·Sufeng ZhangHasan Uludağ
Apr 26, 2007·Macromolecular Bioscience·Sufeng ZhangHasan Uludağ
Feb 9, 2021·Journal of the Egyptian National Cancer Institute·Sujit Arun DesaiPreeti Khulbe

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