Discovery of Peptide-based Bone Morphogenic Protein Mimetics

基于肽的骨形态发生蛋白模拟物的发现

• 批准号: 6993819
• 负责人: PAUL T HAMILTON
• 金额: $ 25.63万
• 依托单位: AFFINERGY ,INC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6993819
• 关键词: biological signal transduction; biomimetics; biotechnology; bone morphogenetic proteins; collagen; drug delivery systems; drug discovery /isolation; growth factor receptors; peptides; phage display; protein binding

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.

描述（由申请人提供）：在此提案中，我们提出了一种新颖的方法，用于识别和固定BMP模拟物。我们计划使用噬菌体显示技术来识别模仿BMP受体的类似BMP信号的肽。这些肽将与先前鉴定的高亲和力，胶原结合肽有关。所得的杂化分子将允许从当前使用的生物材料的表面进行局部递送合成的骨诱导分子。骨形态发生蛋白（BMP）是诱导骨形成的有效分化因子。目前在临床应用中使用了两种重组人BMP，RHBMP-2和RHBMP-7，以促进脊柱融合和断裂 - 裂缝。需要BMP的局部递送来促进治疗部位的愈合，并限制骨骼形成远离现场。由于难以将BMP连接到局部骨骼生长有益的医疗器械表面，例如髋关节植入物或脊柱融合装置，因此这一要求限制了许多BMP的临床应用。使用重组人BMP的第二个限制是费用。与合成治疗剂相比，生物学治疗剂的开发和制造更昂贵。