{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:31:54Z","timestamp":1760297514850},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,7,21]],"date-time":"2005-07-21T00:00:00Z","timestamp":1121904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2005,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chemical conjugation of bisphosphonates (BPs) to proteins is an effective means to enhance binding of proteins to mineral\u2010containing biomaterials. BPs linked to proteins with reversible (i.e., cleavable) linkages were considered desirable over the conjugates linked with stable linkages because cleavable linkages allow protein release in free form from the mineral\u2010containing biomaterials. To explore the feasibility of creating cleavable BP\u2010protein conjugates, an amine\u2010 and a thiol\u2010containing BP were conjugated to the model protein Bovine Serum Albumin (BSA) with <jats:italic>N<\/jats:italic>\u2010succinimidyl\u20103\u2010(2\u2010pyridyldithio)propionate (SPDP), which resulted in disulfide\u2010linked BP\u2013BSA conjugates. Although disulfide\u2010linked conjugates were stable under aqueous conditions, the conjugates in solution were readily cleaved in the presence of physiological concentrations (\u223c 0.3 m<jats:italic>M<\/jats:italic>) of the thiol compound, cysteine. The imparted mineral affinity as a result of BP conjugation, as assessed by hydroxyapatite (HA) binding <jats:italic>in vitro<\/jats:italic>, was lost upon cleavage of the disulfide\u2010linked BP. The conjugates bound to HA were also cleavable with cysteine, but their cleavage rate was significantly reduced as compared to the conjugates in solution. In conclusion, disulfide\u2010linked BP conjugates were shown to be readily cleavable by the amino acid cysteine and this resulted in the loss of imparted mineral affinity of the proteins. The proposed approach will be useful for modulating <jats:italic>in vivo<\/jats:italic> delivery of proteins implanted with mineral\u2010containing biomaterials. \u00a9 2005 Wiley Periodicals, Inc. 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