Iafisco Michele, Palazzo Barbara, Falini Giuseppe, Foggia Michele Di, Bonora Sergio, Nicolis Stefania, Casella Luigi, Roveri Norberto
Dipartimento di Chimica G. Ciamician, Alma Mater Studiorum Università di Bologna, Via Selmi 2, 40126 Bologna, Italy.
Langmuir. 2008 May 6;24(9):4924-30. doi: 10.1021/la703381h. Epub 2008 Mar 29.
The chemical conjugation of bisphosphonates (BPs), specifically alendronate, to hydroxyapatite could be an effective means to impart to it fine-tuned bioactivity. Horse heart myoglobin (Mb), a well-characterized protein, has been adsorbed onto biomimetic hydroxyapatite nanocrystals (nHA) and onto the nHA/alendronate conjugate powdered samples. The obtained materials have potential use in bone implantation and as prospective drug-delivery devices. The kinetic absorption of Mb onto nHA is dramatically affected by its functionalization with alendronate. The covering of the nHA surface by alendronate inhibits the adsorption of myoglobin. The adsorption mechanisms of the protein were studied by spectroscopic techniques (UV-vis and surface-enhanced Raman spectroscopy). The results indicate that the protein changes conformation upon adsorption on the inorganic substrate. In particular, the interaction with nHA alters the coordination state of the iron in the heme through the formation of a hexacoordinated low-spin Mb heme, possibly involving the distal histidine. Instead, the covering of the nHA surface by alendronate does not adsorb the protein but preserves the coordination state of the heme moiety. This study could be of significance either in the field of biomaterials science, in particular, to fine tune a bone-specific drug delivery device and to test nHA as a new support for heterogeneous catalysis, improving the understating of enzyme immobilization.
双膦酸盐（BPs），特别是阿仑膦酸盐与羟基磷灰石的化学共轭可能是赋予其微调生物活性的有效手段。马心肌红蛋白（Mb）是一种特征明确的蛋白质，已被吸附到仿生羟基磷灰石纳米晶体（nHA）以及nHA/阿仑膦酸盐共轭粉末样品上。所获得的材料在骨植入和作为潜在的药物递送装置方面具有潜在用途。Mb在nHA上的动力学吸附受到其用阿仑膦酸盐功能化的显著影响。阿仑膦酸盐对nHA表面的覆盖抑制了肌红蛋白的吸附。通过光谱技术（紫外可见光谱和表面增强拉曼光谱）研究了蛋白质的吸附机制。结果表明，蛋白质在吸附到无机底物上时会改变构象。特别是，与nHA的相互作用通过形成六配位低自旋Mb血红素改变了血红素中铁的配位状态，可能涉及远端组氨酸。相反，阿仑膦酸盐对nHA表面的覆盖不会吸附蛋白质，但保留了血红素部分的配位状态。这项研究在生物材料科学领域可能具有重要意义，特别是在微调骨特异性药物递送装置以及测试nHA作为多相催化的新载体方面，有助于加深对酶固定化的理解。
