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• W2076455738 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 synthesized (6) can serve as a carrier for bone delivery while reducing the extent of protein modification necessary for bone targeting. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2788–2799, 2004" @default.
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• W2076455738 date "2004-11-01" @default.
• W2076455738 modified "2023-10-15" @default.
• W2076455738 title "A di(bisphosphonic acid) for protein coupling and targeting to bone" @default.
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• W2076455738 doi "https://doi.org/10.1002/jps.20186" @default.
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