HEPARIN BINDING PEPTIDES FROM CELL ADHESION PROTEINS

描述：研究的具体目的是阐明 肝素结合中所涉及的相互作用的肽从 细胞粘附蛋白纤连蛋白、层粘连蛋白、玻连蛋白和 血小板反应蛋白最初的研究将集中在肽从 纤连蛋白，包括与表面受体结合的肽 高转移性小鼠黑色素瘤细胞。 研究将涉及 母体肽、肽类似物、肝素和肝素- 衍生的寡糖。 目的是鉴定肽和 具有结合倾向的肝素基序，以确定是否结合 涉及位点特异性或离域静电相互作用， 根据结合常数确定结合强度， 表征肝素-肽复合物的结构特征。 这些目标将利用从以下方面获得的信息来实现： 核磁共振（NMR）光谱。的动机 提出的研究是，细胞粘附过程的中断， 合成肽和/或寡糖具有作为 治疗性干预（抗粘连治疗） 细胞粘附在其中起关键作用的疾病。 比如说， 细胞粘附蛋白的肝素结合片段可以抑制 几种肿瘤的实验性转移，肝素可以抑制 人类免疫缺陷病毒1型（HIV-1）的复制。 长 术语目标是，在分子水平上， 肝素与肽结合中涉及的相互作用， 从来自细胞粘附的细胞粘附结构域的肽开始 proteins. 获得的知识具有临床意义，因为它 将为设计新的合成药物提供基础 具有甚至更高的选择性和特异性的肽用于抗- 粘连疗法

DESCRIPTION: The specific aims of the research are to elucidate the interactions involved in the binding of heparin by peptides from the cell adhesion proteins fibronectin, laminin, vitronectin and thrombospondin. The initial research will focus on peptides from fibronectin, including peptides which bind to receptors on the surface of highly metastatic mouse melanoma cells. The research will involve studies of the parent peptides, peptide analogs, heparin and heparin- derived oligosaccharides. The objectives are to identify peptide and heparin motifs with a propensity for binding, to determine if binding involves site specific or delocalized electrostatic interactions, to determine the strength of binding in terms of binding constants and to characterize structural features of the heparin-peptide complexes. These objectives will be achieved using information obtained from nuclear magnetic resonance (NMR) spectroscopy. The motivation for the proposed research is that interruption of the cell adhesion process with synthetic peptides and/or oligosaccharides has potential as a therapeutic intervention (anti-adhesion therapy) in the development of diseases in which cell adhesion plays a critical role. For example, heparin binding fragments of cell adhesion proteins can inhibit the experimental metastasis of several tumors and heparin can inhibit the replication of human immunodeficiency virus type-1 (HIV-1). The long term objectives are to characterize, in detail at the molecular level, the interactions involved in the binding of peptides by heparin, starting with peptides from the cell adhesion domains of cell adhesion proteins. The knowledge to be gained is of clinical interest because it will provide a fundamental basis from which to design new synthetic peptides with even greater selectivity and specificity for use in anti- adhesion therapy.