Discovery of Peptide-based Bone Morphogenic Protein Mimetics

描述（由申请人提供）：在本提案中，我们提出了一种识别和固定BMP模拟物的新方法。我们计划使用噬菌体展示技术来鉴定模仿BMP样BMP受体信号的肽。这些肽将连接到先前确定的高亲和力胶原结合肽。由此产生的混合分子将允许从当前使用的生物材料表面控制局部递送合成的骨诱导分子。骨形成蛋白（BMPs）是诱导骨形成的有效分化因子。两种重组人bmp蛋白，rhBMP-2和rhBMP-7，目前用于临床应用，以促进脊柱融合和骨折愈合。BMP的局部递送是促进治疗部位愈合和限制骨形成远离该部位的必要条件。这一要求限制了许多BMP的临床应用，因为很难将BMP直接附着在有利于局部骨生长的医疗器械表面，如髋关节植入物或脊柱融合装置。使用重组人bmp的第二个限制是费用。生物疗法的开发和制造比合成疗法更昂贵。

DESCRIPTION (provided by applicant): In this proposal, we present a novel approach for the identification and immobilization of a BMP mimetic. We plan to use phage display technology to identify peptides that mimic BMP-like signaling of the BMP receptors. These peptides will be linked to a previously identified high-affinity, collagen-binding peptide. The resulting hybrid molecule will allow controlled, local delivery of a synthetic, osteoinductive molecule from the surface of a currently employed biomaterial. Bone Morphogenic Proteins (BMPs) are potent differentiation factors that induce bone formation. Two recombinant human BMPs, rhBMP-2 and rhBMP-7, are currently used in clinical applications to promote spinal fusion and fracture-healing. Localized delivery of BMP is required to promote healing at the treatment site and restrict bone formation away from the site. This requirement limits the clinical applications of many BMPs due to the difficulty in attaching a BMP directly to the surface of a medical device where localized bone growth is beneficial, such as a hip implant or spinal fusion device. A second limitation for the use of recombinant human BMPs is the expense. Biologic therapeutics are more expensive to develop and manufacture than synthetic therapeutics.