TRACHEOBRONCHIAL GLYCOPROTEIN STRUCTURE

在这项提议中，我们的目标是在化学和结构上表征 纯化的人气管、支气管糖蛋白。重点放在 主要酸性硫酸低聚糖和主要低聚糖的分析 气管、支气管寡糖-寡肽亚基的分离 糖蛋白。硫酸化低聚糖的表征研究 压力，因为主要是这一部分随着严重程度的增加而增加 是一种肺部疾病。气管、支气管糖蛋白及其分离组份 来自患有各种形式的慢性阻塞性疾病的患者 肺部疾病(如慢性支气管炎、哮喘、支气管扩张症、 将对肺泡蛋白沉着症和囊性纤维化(CF)进行研究、绘制和 比较，以便从不同的病理载体了解如何 气管、支气管腺黏膜下腺改变其分泌性糖蛋白 结构，以应对慢性病。重音也放在 不同低聚糖-寡肽亚基的分离分析 气管、支气管糖蛋白。我们的初步研究强烈表明 在编码的蛋白质核心中有确定的氨基酸序列 用于连接的寡糖的硫酸盐化或唾液酸化，以及 是糖苷类低聚糖的不同类型 与丝氨酸和苏氨酸相连。气-液色谱与质谱学 光谱分析将用于所有化学研究，并将包括新的 本实验室开发的硫酸盐、糖的分析方法 硫酸盐、唾液酸、氨基糖和氨基酸。 这些糖蛋白的阴离子性增加可能在 慢性肺病是它使他们更不容易患上 细菌的酶降解。我们建议通过以下方式对此进行调查 体外研究气管、支气管糖蛋白的耐药性， 具有不同程度的硫酸盐化，对糖苷酶攻击。 到目前为止，我们对它的结构和相关知识知之甚少 气管、支气管糖蛋白的功能。在过去五年中，我们 已经分离和纯化了所有的气管和支气管糖蛋白，以及 其中的一小部分，将用于本提案。他们的研究将提供 关于结构和生物化学的重要和需要的信息 这些在健康和疾病中非常重要的分子。

Our aim, in this proposal, is to chemically and structurally characterize purified human tracheobronchial glycoproteins. Emphasis is placed on analyzing the major acidic sulfated oligosaccharides and major oligosaccharide-oligopeptide subunits isolated from tracheobronchial glycoproteins. Research on characterizing the sulfated oligosaccharides is stressed since it is primarily this fraction that increases with severity of a lung disease. Tracheobronchial glycoproteins and isolated fractions from patients suffereing from various forms of chronic obstructive pulmonary disease (e.g., chronic bronchitis, asthma, bronchiectasis, alveolar proteinosis and cystic fibrosis (CF) will be studied, mapped and compared so as to gain insight from different pathological vectors on how the tracheobronchial submucosal glands alter their secretory glycoprotein structure in response to chronic disease. Accent is also placed on analyzing the different oligosaccharide-oligopeptide subunits isolated from tracheobronchial glycoproteins. Our preliminary studies strongly suggest that there is definite amino acid sequence in the protein core that codes for sulfation or sialation of the attached oligosaccharide and that there is a difference in the type of oligosaccharide that is glycosidically linked to serine and to threonine. Gas-liquid chromatography and mass spectrometry will be employed in all chemical studies and will include new methods, developed in this laboratory, for the analysis of sulfate, sugar sulfates, sialic acids, amino sugars and amino acids. One possible role for the increased anionicity of these glycoproteins in chronic lung disease is that it renders them to be less susceptible to bacterial enzymatic degradation. We propose to investigate this by studying in vitro the resistance of tracheobronchial glycoproteins, possessing varying degrees of sulfation, to glycosidase attack. To date, we have very little knowledge of the structure and related functions of tracheobronchial glycoproteins. Over the past five years we have isolated and purified all the tracheobronchial glycoproteins, and fraction thereof, to be used in this proposal. Their study will provide important and needed information about the structure and biochemistry of these very important molecules in health and disease.