Osteotropic peptide that differentiates functional domains of the skeleton
Osteotropic peptide that differentiates functional domains of the skeleton
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DOI：
10.1021/bc7002132
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发表时间：
2007-09-01
影响因子：
4.7
通讯作者：
Kopecek, Jindrich
中科院分区：
文献类型：
--
作者：
Wang, Dong;Miller, Scott C.;Kopecek, Jindrich
已发现 HPMA 共聚物-D-天冬氨酸八肽 (D-Asp(8)) 缀合物在全身给药后可靶向整个骨架。在最近一项使用去势大鼠骨质疏松模型的研究中，我们惊讶地发现 D-Asps 可以有利地识别骨骼组织中的吸收位点，而另一个骨靶向部分阿仑膦酸钠 (ALN) 则将递送系统引导至形成和吸收位点。原子力显微镜 (AFM) 分析表明，ALN 与羟基磷灰石 (HA) 的结合力比 D-Asp(8) 更强。体外 HA 结合研究表明，D-Asp(8) 对 HA 结晶度的变化比 ALN 更敏感。由于新形成的骨（形成位点）中的骨磷灰石通常比骨吸收位点（主要是成熟骨）具有较低的结晶度，因此我们认为D-Asp（8）对骨吸收位点的有利识别可能归因于与双磷酸盐相比，其与磷灰石的结合相对较弱，以及骨磷灰石在骨骼的不同功能域的结晶度不同。
HPMA copolymer-D-asparti c acid octapeptide (D-Asp(8)) conjugates have been found to target the entire skeleton after systemic administration. In a recent study using the ovariectornized rat model of osteoporosis, we surprisingly discovered that D-Asps would favorably recognize resorption sites in skeletal tissues, while another bone-targeting moiety, alendronate (ALN), directs the delivery system to both formation and resorption sites. Atomic force microscopy (AFM) analyses reveal that ALN has a stronger binding force to hydroxyapatite (HA) than D-Asp(8). In vitro HA binding studies indicate that D-Asp(8) is more sensitive to change of HA crystallinity than ALN. Because the bone apatite in the newly formed bone (formation sites) usually has lower crystallinity than the resorption sites (mainly mature bone), we believe that the favorable recognition of D-Asp(8) to the bone resorption sites could be attributed to its relatively weak binding to apatite, when compared to bisphosphonates, and the different levels of crystallinity of bone apatite at different functional domains of the skeleton.