Discovery of Peptide-based Bone Morphogenic Protein Mimetics

描述(由申请人提供)：在这项提案中，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识别模拟BMP受体的BMP样信号的多肽。这些多肽将与先前发现的一种高亲和力的胶原蛋白结合肽相连。由此产生的杂化分子将允许从目前使用的生物材料的表面控制地、局部地输送合成的骨诱导分子。骨形态发生蛋白(BMPs)是诱导骨形成的有效分化因子。两种重组人骨形成蛋白，即重组人骨形态发生蛋白-2和重组骨形态发生蛋白-7，目前被用于临床应用，以促进脊柱融合和骨折愈合。需要局部注射BMP以促进治疗部位的愈合，并限制远离治疗部位的骨形成。这一要求限制了许多BMP的临床应用，因为很难将BMP直接附着到局部骨生长有益的医疗设备的表面，例如髋关节植入物或脊柱融合设备。使用重组人骨形态发生蛋白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.