HEPARIN BINDING PEPTIDES FROM CELL ADHESION PROTEINS

描述：这项研究的具体目的是阐明 肝素与肝素结合的相互作用 细胞黏附蛋白纤维连接蛋白、层粘连蛋白、玻璃体连接蛋白和 凝血酶敏感蛋白。最初的研究将集中在来自于 纤维连接蛋白，包括与表面受体结合的多肽 高转移性小鼠黑色素瘤细胞。这项研究将涉及 母体多肽、多肽类似物、肝素和肝素的研究 衍生低聚糖。目标是鉴定多肽和 具有结合倾向的肝素基序，以确定是否结合 涉及特定位置或离域的静电相互作用，以 根据结合常数和TO来确定结合强度 表征肝素-多肽复合体的结构特征。 这些目标将使用从以下渠道获得的信息来实现 核磁共振(核磁共振)光谱。其动机是 建议的研究是，中断细胞黏附过程与 合成肽和/或低聚糖具有潜在的 治疗干预(抗粘连疗法)在发展中的作用 细胞黏附起关键作用的疾病。例如, 肝素结合片段的细胞黏附蛋白可以抑制 几种肿瘤的实验性转移和肝素可抑制 人类免疫缺陷病毒1型(HIV-1)的复制。《长河》 学期目标是在分子水平上详细描述， 肝素与多肽结合中的相互作用， 从细胞黏附区的多肽开始细胞黏附 蛋白质。将获得的知识具有临床意义，因为它 将为设计新的合成材料提供基本的基础 具有更高的选择性和特异性的多肽用于抗- 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.